Each year, The Patient Story attends a handful of cancer conferences to meet with experts on the frontlines of cancer care and report on developments that matter to patients. We’ve reported on ASH, SABCS, and ASCO. But what exactly is ASCO, and why should patients care about an annual conference for medical professionals?
The American Society for Clinical Oncology (ASCO), established in 1964, plays a pivotal role in the global fight against cancer. It unites over 40,000 professionals from more than 100 countries across various oncology subspecialties and disciplines around the world, creating a comprehensive network of experts committed to advancing cancer care. This premier organization is at the forefront of fostering innovative research, disseminating critical educational resources, and advocating for high-quality patient care. By emphasizing a multidisciplinary approach, ASCO ensures that its members are well-equipped to handle the complexities of oncology, thereby enhancing patient outcomes and contributing to the reduction of cancer’s worldwide impact.
ASCO’s strategic objectives are focused on accelerating the pace of cancer research, optimizing educational opportunities for oncology professionals, and improving patient care through the integration of the latest scientific discoveries and treatment modalities. The society leverages its extensive network and resources to support initiatives that drive progress in cancer treatment and care delivery. For instance, ASCO’s annual meeting serves as a global platform for sharing groundbreaking research findings and discussing innovative treatment approaches, reflecting the society’s commitment to bringing the benefits of cutting-edge cancer research to patients and practitioners alike. Through such endeavors, ASCO not only facilitates the dissemination of vital knowledge within the oncology community but also significantly contributes to the overarching goal of diminishing the global cancer burden.
The American Society for Clinical Oncology (ASCO) plays a crucial role in transforming the landscape of cancer care by pushing for legislative reforms aimed at eliminating obstacles to high-quality cancer treatment. By advocating for changes in healthcare policies and practices, ASCO ensures that cancer care becomes more accessible and equitable for patients across the globe. These efforts are particularly vital in addressing disparities in cancer treatment and ensuring that all patients, regardless of their socioeconomic status, have access to the latest and most effective therapies.
Moreover, ASCO places a strong emphasis on the value of open, honest communication and the establishment of a continuous, trusting relationship between oncologists and their patients. This philosophy is fundamental to delivering patient-centered care, which prioritizes the preferences, needs, and values of patients and their families. By fostering a care environment that is both compassionate and comprehensive, ASCO influences the treatment journey of cancer patients in profound ways. It ensures that the care provided is not only technically advanced but also emotionally supportive, thereby enhancing the overall quality of life for patients during their treatment journey. Such an approach has been shown to improve patient outcomes and satisfaction, illustrating ASCO’s pivotal role in making cancer care more patient-centered and effective.
Cancer clinical trials are pivotal to the advancement of cancer care, serving as the primary method through which new treatments are developed, tested, and perfected. The American Society for Clinical Oncology (ASCO) champions these trials, recognizing their indispensable role in pushing the boundaries of medical science to discover more effective cancer therapies. By rigorously evaluating the safety and efficacy of novel treatments, clinical trials contribute significantly to enhancing patient care options and outcomes. They are the stepping stones that lead to the approval of new drugs, therapies, and treatment protocols that can offer hope to millions of patients worldwide. The ASCO Hub provides information on clinical oncology.
ASCO actively encourages participation in clinical trials among cancer patients, emphasizing the dual benefits of gaining access to cutting-edge treatments while contributing to vital research that can save lives in the future. This encouragement is based on the understanding that clinical trials are essential not only for the individual patient’s potential benefit but also for the collective progress in the fight against cancer. A notable example of this is the development of targeted therapies, which have revolutionized cancer treatment by focusing on specific genetic mutations within cancer cells, significantly improving patient outcomes in certain cancer types. Participation in clinical trials also empowers patients by placing them at the heart of their own care, making them active contributors to the advancement of medical knowledge and the quest for a cure.
ASCO conferences serve as pivotal arenas where the latest in cancer research is unveiled, offering insights into groundbreaking therapies, innovative treatment approaches, and the newest trends sweeping through the field of oncology. These conferences act as melting pots of knowledge, bringing together the brightest minds in cancer research from across the globe. They facilitate an essential exchange of information and foster partnerships that are critical in propelling the advancement of cancer care. One notable example is the introduction of novel immunotherapy treatments which have revolutionized how certain types of cancer are treated, showcasing the potential to significantly enhance patient survival rates and quality of life.
Moreover, recent ASCO meetings have spotlighted the strides made in precision medicine and personalized treatments, marking a shift towards more tailored and effective care strategies. These advancements underscore the importance of understanding the genetic makeup of an individual’s cancer, allowing for therapies that are specifically designed to target the mutations driving the disease. We recently interviewed Dr. Cathy Eng, the David H. Johnson Endowed Chair in Surgical and Medical Oncology at Vanderbilt-Ingram Cancer Center on the latest advances in colorectal cancer treatments and clinical trials and the use of biomarkers. This approach of using the genetic makeup of a person’s specific disease not only improves the efficacy of treatments but also minimizes the side effects, presenting a beacon of hope for patients who previously had limited options. The breakthroughs shared at ASCO conferences exemplify the relentless pursuit of knowledge and innovation in the oncology community, offering new avenues for diagnosis, treatment, and ultimately, the cure of cancer.
The escalating expenses associated with cancer treatment present a formidable challenge, affecting not only patients but also their families, healthcare providers, and the broader healthcare infrastructure. In response to this critical issue, the American Society for Clinical Oncology (ASCO) established the Cost of Care Task Force. This initiative focuses on exploring and advocating for effective strategies to alleviate the financial strain imposed by cancer care on patients and the healthcare system at large. By prioritizing cost-conscious care practices, ASCO is committed to ensuring that financial considerations do not detract from the quality or accessibility of patient outcomes. For example, ASCO promotes the integration of discussions about the cost of care into treatment planning conversations, enabling patients and their families to make choices that align with both their healthcare needs and financial realities.
Moreover, ASCO’s collaborative efforts with other stakeholders in the cancer care ecosystem are pivotal in developing and disseminating resources aimed at educating patients about the financial dimensions of cancer treatment. These resources are designed to empower patients with the knowledge they need to navigate the complexities of cancer care financing, from understanding insurance coverage to exploring assistance programs. By fostering an informed patient community, ASCO enhances the capacity of individuals to make treatment decisions that are both medically and economically sound. This approach not only supports patients in managing their care but also contributes to the broader goal of making high-quality cancer treatment more accessible and sustainable for all involved parties.
ASCO’s Initiatives for Evidence-Based Decision Making
The American Society for Clinical Oncology (ASCO) takes a leadership role in fostering evidence-based decision-making within the oncology community. Through pivotal initiatives like the “Choosing Wisely” campaign, ASCO seeks to curtail the prevalence of unnecessary diagnostic and therapeutic procedures in cancer care. This campaign encourages both oncologists and patients to engage in open discussions about the necessity and potential value of specific interventions, thereby ensuring that each patient receives care that is not only effective but also directly aligned with their unique health circumstances and treatment goals. For example, ASCO’s guidelines advise against the routine use of advanced imaging technologies in the early staging of certain cancers where evidence does not support their benefit, emphasizing the importance of individualized care planning based on robust clinical evidence.
Moreover, ASCO’s commitment to evidence-based practices extends to the development and dissemination of comprehensive clinical guidelines. These guidelines serve as a valuable resource for oncologists, providing them with the latest research findings and expert consensus on the most effective approaches to cancer treatment and care. By prioritizing interventions that have been rigorously evaluated and proven to enhance patient outcomes, ASCO not only advances the quality of care but also contributes to the sustainability of healthcare systems by mitigating unnecessary costs associated with ineffective or marginally beneficial treatments. This dual focus on improving patient care and optimizing resource use reflects ASCO’s holistic approach to addressing the complexities of cancer treatment in the modern healthcare environment.
Membership and Resources
Membership in ASCO provides oncology professionals with unparalleled access to a comprehensive suite of educational materials, the latest scientific publications, and exclusive networking opportunities. This membership is designed to support their ongoing professional growth and ensure they remain at the forefront of oncology practice and research. By joining ASCO, members gain entry into a dynamic community committed to the continuous advancement of cancer care. They are provided with tools and resources necessary to navigate the complexities of modern oncology, including guidelines for evidence-based practice, updates on the latest research findings, and opportunities to participate in groundbreaking clinical trials.
Furthermore, ASCO’s global network offers a unique platform for collaboration and knowledge exchange among cancer care professionals from around the world. This network fosters mentorship opportunities, encourages the sharing of best practices, and facilitates partnerships that can lead to innovative solutions in cancer treatment and patient care. For instance, through ASCO’s annual meetings and specialized conferences, members can connect with peers, discuss the latest trends and breakthroughs in oncology, and contribute to the global effort to conquer cancer. This vibrant community not only enhances the professional journey of its members but also significantly impacts the quality of care provided to patients worldwide.
ASCO’s Commitment to Patients
The American Society for Clinical Oncology (ASCO) stands at the forefront of transforming cancer care and patient experience through its persistent dedication to research, education, and the implementation of patient-centered practices. This commitment is evident in ASCO’s active role in pioneering innovations that drive significant improvements in treatment outcomes and quality of life for individuals facing cancer. By fostering a holistic approach that spans from the latest breakthroughs in oncology research to the intricacies of patient care, ASCO ensures a supportive and informed journey for patients and their families. This includes not only access to cutting-edge treatments but also the provision of comprehensive resources designed to empower patients with knowledge and support at every stage of their cancer journey.
Furthermore, ASCO’s initiatives extend beyond clinical advancements, addressing critical aspects such as the cost of care, the importance of evidence-based decision making, and the advocacy for policies that benefit the cancer community at large. One notable example of ASCO’s impact is its involvement in the “Choosing Wisely” campaign, aimed at reducing unnecessary treatments and procedures, thus optimizing patient care and resource utilization. Through these efforts, ASCO demonstrates a deep-seated commitment to not only enhancing the therapeutic landscape but also ensuring that patients navigate their treatment with dignity, respect, and access to the best possible care options. This multifaceted dedication underscores ASCO’s pivotal role in the ongoing fight against cancer, making it a beacon of hope and a source of strength for patients, their families, and the oncology community.
You’re an advocate. You’re an advocate for yourself… Everybody has a place and everybody has a role.
Where is Hodgkin lymphoma headed in 2024? Two-time Hodgkin’s lymphoma survivor Dr. Sam Siegel discusses with top lymphoma experts, Dr. Natalie Grover of UNC Health and Dr. Stephen Ansell of Mayo Clinic, as they break down what patients and caregivers need to know!
Key topics include the latest treatment options and clinical trials, reducing toxicity from treatments, advances in post-transplant relapse, and the roles of CAR T-cell therapy and bispecific antibodies in the treatment of Hodgkin lymphoma.
Thank you to Pfizer for its support of our patient education program! The Patient Story retains full editorial control over all content.
This interview has been edited for clarity and length. This is not medical advice. Please consult with your healthcare provider for treatment decisions.
Stephanie Chuang, The Patient Story: My name is Stephanie Chuang, the founder of The Patient Story. I also got a blood cancer diagnosis a few years ago. Mine was non-Hodgkin lymphoma, but we have so many shared experiences in what we’re looking for and that’s what The Patient Story is all about.
We help both patients and care partners navigate a cancer diagnosis. We do this primarily through in-depth conversations with patients, care partners, and top cancer specialists.
I also want to give special thanks to Seagen for supporting our educational program. Their support helps programs like this become more available and free for our audience. We want to note that The Patient Story retains full editorial control of this entire program and that this is not meant to be a substitute for medical advice.
Our patient moderator, Dr. Sam Siegel, will be leading the conversation from this point forward.
Sam Siegel, MD, Patient Advocate
Dr. Sam Siegel: Thanks, Stephanie! I’m a two-time Hodgkin’s lymphoma survivor, bone marrow transplant survivor, and primary care physician doing survivorship medicine. I’m here to have this wonderful conversation with Dr. Natalie Grover and Dr. Stephen Ansell about Hodgkin lymphoma updates.
Natalie Grover, MD
Sam: Dr. Natalie Grover is a hematologist-oncologist at the UNC School of Medicine. She’s the clinical director of the cellular therapy program, leads several CAR T-cell therapy clinical trials in lymphoma, and strives to improve treatment options and quality of life for lymphoma patients.
Dr. Grover, can you tell us a little bit about yourself, what drew you to lymphoma, and about your approach to patients and how you care for them?
Dr. Natalie Grover: I was drawn to oncology as a maternal medicine resident. Much of it was based on my relationship with patients whom I saw in the inpatient oncology ward. When I saw those patients, I always wanted to go back and find out more about what happened to them and form connections with them.
There were so many discoveries and new treatments available. Even during residency, the treatment landscape was changing so much and that drove me to oncology.
I like how heterogeneous lymphoma is and how it involves a wide patient population of both young and older patients. It’s truly a systemic disease. There are so many different types of lymphoma so my clinic is a very heterogeneous mix of different patients and I enjoy that.
Sam: That makes a lot of sense. Lymphoma is the umbrella, but it’s a lot of different diseases that can affect multiple parts of the body. I could see how that’s interesting.
Stephen Ansell, MD, PhD
Sam: Dr. Stephen Ansell is a hematologist-oncologist at the Mayo Clinic who studies and specializes in Hodgkin’s lymphoma. His research has led to the use of immune checkpoint therapy in lymphomas, which is a very exciting development. His goal is to translate his research into new treatment approaches.
Dr. Ansell, can you tell us about your path into lymphoma, what drew you to the field, and your approach to patients?
Dr. Stephen Ansell: I trained in South Africa. I was very focused on internal medicine, but they needed someone to do some work temporarily in oncology and assigned me.
When I got there, similar to Dr. Grover, I was excited about the opportunity, the disease, the patients, and how we could make a difference based on the fact that treatments were highly effective and beneficial. Patients benefited substantially even from initial treatments back in the day of more chemotherapy.
What has been exciting for me throughout my career has been to see how we can change treatments by increasing the number of people who benefit and hopefully get cured, and decreasing the side effects and toxicities by being able to find effective therapies that aren’t that hard on patients.
Sam: Your areas of interest and passion are so personally meaningful to me and my lymphoma journey, and I think will resonate with a lot of people.
Even though I had some side effects from the brentuximab at the highest dose that I first started it on, it still felt like a cakewalk compared to my initial drug regimen.
Dr. Sam Siegel
Sam’s Hodgkin Lymphoma Story
Sam: I was diagnosed with stage 2AE Hodgkin’s lymphoma and the reason that 2AE is important is because E means extranodal manifestations. I had some lung involvement and it was confusing whether or not I was a stage 2 with right around the lymph nodes in that lung or stage 4. That was going to impact how many months of chemotherapy I would have.
I started with ABVD chemotherapy. Within two months, the initial cough that I had at the time of diagnosis improved pretty quickly. Towards the end of those two months, I started getting a cough again. My PET scan looked good so the thought was that bleomycin was probably to blame for that cough.
We dropped bleomycin and it felt pretty okay making that decision. I suspected that something else was going on, but because the scan had come back clean, we decided to watch and wait.
About a month or two after that, I developed symptoms that were eerily reminiscent of my initial diagnosis, such as wheezing in the upper left side of my chest, which I knew wasn’t normal, and a pea-sized lump above my collarbone in a very similar location to where the initial lump was.
I suspected that those were Hodgkin lymphoma symptoms and sought care right away. The PET scan showed that I was most likely having a relapse.
It was a process to get the tissue to confirm the relapse. I had to have three biopsies, with the third one involving a thoracic surgery to get a lymph node right near my heart.
By that time, I felt so beaten up by traditional cytotoxic chemotherapy. New information was coming around about salvage therapy, which is the therapy after a person has relapsed from initial therapy. At that time, I didn’t feel that I could go through another few months of multi-drug traditional cytotoxic chemotherapy.
Data was coming out about brentuximab, an antibody-drug conjugate, and using that as a bridge to autologous bone marrow transplant. My oncologist said, “These trials showed that this could be an effective bridge to transplant. What do you think?” I said yes because I wanted to go for the therapy with the least amount of toxicity.
Even though I had some side effects from the brentuximab at the highest dose that I first started it on, it still felt like a cakewalk compared to my initial drug regimen.
That goes to show how important the science is and the clinical trials that inform oncologists how to adjust therapies, especially therapies that were traditionally pretty toxic in terms of long-term and late-term effects.
There are always ways in which we’re trying to make treatment better… we’re trying to replace radiation therapy by utilizing new agents.
Dr. Stephen Ansell
Standard of Care: First-Line Treatments
Sam: Dr. Ansell, can you tell us about the current standard first-line treatments and their efficacy for Hodgkin lymphoma?
Dr. Ansell: In many respects, we think about it in two buckets: people who have more limited-stage disease (only on one side of the diaphragm, either above or below) or advanced-stage disease (both sides of the diaphragm, in the bone marrow, or other tissues).
With limited-stage disease, we again think of two buckets. These are different symptoms and other tests to determine prognostic factors. If you have favorable prognostic factors, we treat you with very minimal chemotherapy. If you have more symptoms and unfavorable factors, we will treat you with a little bit more treatment. If you have advanced disease, we give you more treatment yet again.
There are always ways in which we’re trying to make treatment better, but the most standard way is if you have very limited disease with good favorable factors, we often will give two rounds of chemotherapy treatment and then consider consolidation radiation treatment.
If you have a more advanced disease, still limited to one side of the diaphragm but with more unfavorable factors, we would give more chemotherapy and more radiation treatment. Then for advanced-stage disease, we would give chemotherapy and no radiation treatment.
However, we’re trying to replace radiation therapy by utilizing new agents. We’ve used PET scans to tell us who might need extra treatment or not. I have to hedge a little bit because a lot of it is individualized and that’s the most important thing.
It’s so important to raise awareness about the importance of being involved in clinical trials and knowing that you don’t have to have failed multiple lines of therapy before you consider them.
Dr. Sam Siegel
Sam: Absolutely. How do you decide? There are different prognostic systems so if somebody is unfavorable in one and favorable in others, how do you factor that in?
Dr. Ansell: Pick one system and utilize the data supported by that system. The German Hodgkin Study Group has done a lot of work in this space. In our practice, we tend to use the prognostic system that they use because that helps us standardize treatment.
What we want to do is always push the envelope. We encourage people to participate in clinical trials that are testing new ways compared to the standard ways to see if we can optimize treatment even further.
Sam: I love that. Thank you for bringing up clinical trials. It’s so important to raise awareness about the importance of being involved in clinical trials and knowing that you don’t have to have failed multiple lines of therapy before you consider them.
Clinical trials can be for everyone and there are so many different types of situations where somebody could need a clinical trial. We’re looking at things to de-escalate therapy or alter treatments based on a patient’s situation.
Dr. Ansell: I would say you’re exactly right. The most impressive and important data that has come out on Hodgkin lymphoma is in the front line based on recent clinical trials. Everyone needs to remember that what we do currently is based on people who have participated in clinical trials that have changed how we practice.
Standardly, we utilize new agents, like PD-1 blocking antibodies or brentuximab vedotin plus chemotherapy, rather than chemotherapy alone because that’s improved the outcome of patients. Especially in advanced-stage patients, that’s now the standard of care.
The two biggest drugs that have transformed the care for Hodgkin lymphoma in the past 5 to 10 years are brentuximab vedotin… and checkpoint inhibitors.
Dr. Natalie Grover
Latest Advancements in Treatments
Sam: Dr. Grover, what are some of the newest and hottest treatments for Hodgkin lymphoma?
Dr. Grover: I think the hottest advances in Hodgkin lymphoma are related to incorporating some of these new treatments into earlier lines of therapy to try to both improve outcomes so increase the chance of cure and reduce long-term toxicities.
The two biggest drugs that have transformed the care for Hodgkin lymphoma in the past 5 to 10 years are brentuximab vedotin, which is an antibody-drug conjugate. It delivers chemotherapy specifically to the cancer cells.
The cancer cells in Hodgkin lymphoma have a marker on them—CD30—that’s pretty much universally seen in all the Reed-Sternberg cells, the cancer cells in Hodgkin lymphoma. Brentuximab specifically targets those.
The other drugs are what people may have heard of called checkpoint inhibitors. These immunotherapies help the immune system fight Hodgkin’s lymphoma.
When they incorporated these drugs—nivolumab, pembrolizumab, and brentuximab—they were successful in relapsed/refractory disease. Now they’re being moved to earlier lines of therapy to try to reduce the amount of chemotherapy that we’re giving patients and hopefully to enhance care in these patients.
By limiting chemotherapy and radiation, can you improve patient outcomes?
Dr. Natalie Grover
Sam: How about some recent clinical trials for reducing toxicity? I heard about AHOD2131.
Dr. Grover: There’s a clinical trial for pediatric and adult patients looking at whether we can incorporate these newer treatments, brentuximab and checkpoint inhibitors, in newly diagnosed Hodgkin lymphoma patients.
Everyone gets two cycles of standard chemotherapy then patients get randomized to either getting these new treatments, brentuximab and nivolumab, or continuing to standard chemotherapy.
The question is: by limiting chemotherapy and radiation, can you improve patient outcomes? One thing they want to look at is cure rates and long-term survival from a Hodgkin’s standpoint, but they’re also collecting data looking at quality of life patient-reported outcomes.
The top priority is curing their lymphoma, but we also want to think about the quality of life for patients moving forward and making sure that they live long lives.
Dr. Natalie Grover
Sam: That’s incredible. When you’re talking about late-term effects or reducing toxicities, what are some of the things that we’re trying to reduce long-term?
Dr. Grover: One of the chemotherapy drugs that we give patients can affect their heart function so some of the things that we think about are the risk of heart disease down the line.
One of the drugs that we’re using a lot less often now can affect lung function so we look at issues with lung function past therapy.
With some of these drugs and using more brentuximab, another thing that we’re thinking about is neuropathy. Patients can have some nerve damage and issues with pain, numbness, and tingling or doing different functions, like texting, typing, or writing.
With young patients, another thing we think about is fertility. Even though many of these patients can have children in the future as a lot of these earlier treatments don’t have as big an effect on fertility, it’s still something we think about, especially if we need to escalate people who have a disease that relapses or need more aggressive therapies.
We also think of secondary cancers. Some chemotherapy and radiation may increase the risk of having other cancers.
The positive is that most of these patients live long enough for us to focus on that and think about these effects. The top priority is curing their lymphoma, but we also want to think about the quality of life for patients moving forward and making sure that they live long lives.
Checkpoint inhibitors help the immune system fight the cancer. Some of these patients may stop responding to checkpoint inhibitors so there’s interest in using other types of treatments in combination.
Dr. Natalie Grover
Sam: What about trials to re-sensitize to PD-1 drugs? What does that mean?
Dr. Grover: Checkpoint inhibitors are effective in Hodgkin lymphoma. Right now, we’re moving them to earlier lines of therapy but these are treatments that can also work well for relapsed and refractory patients.
Hodgkin lymphoma is unique because, compared to other lymphomas, there aren’t that many cancer cells in these patients. When pathologists look at cells, there are a lot of immune cells around the cancer cells so there aren’t that many lymphoma cells. A lot of it is your immune reaction to the lymphoma.
Checkpoint inhibitors help the immune system fight the cancer. Some of these patients may stop responding to checkpoint inhibitors so there’s interest in using other types of treatments in combination. If a patient progresses on pembrolizumab or nivolumab, can you combine them with other treatments and re-sensitize your immune system so they can be sensitive again to these treatments? There’s some research looking into that.
We’ve also seen patients get the reverse. These treatments may reset the patients in some way. Patients may get checkpoint inhibitors and then after that may respond better to other treatments. There have been some studies showing that after checkpoint inhibitors, even if they progress on those drugs, patients potentially respond better to chemotherapy or other treatments.
Sam: We’re still learning how these drugs impact the immune system and how they might make you respond better to traditional chemotherapies, even if you didn’t initially. That’s incredible.
Dr. Grover: The current biggest advances are in advanced-stage Hodgkin lymphoma. More recently, brentuximab was incorporated in addition to chemotherapy. Dr. Ansell was part of that study. That improved overall survival in advanced-stage Hodgkin lymphoma patients compared to standard of care.
We can see the progression from old-style chemotherapy to immune checkpoint plus chemotherapy as the front-line treatment.
Dr. Stephen Ansell
Early vs. Advanced Stage Advancements
Sam: Dr. Ansell, can you tell us about the SWOG S1826 trial and what that showed?
Dr. Ansell: Picking up again on the theme of better therapies getting better outcomes and using some of the new drugs that we’ve touched on, as Dr. Grover said, the management of advanced-stage patients has moved over time.
Back in the day, we gave ABVD chemotherapy and tried to leave out bleomycin, which causes lung toxicity, if patients were doing well based on PET scans.
These new drugs, brentuximab vedotin being the first one, were brought into the combination in place of bleomycin. It’s now brentuximab with AVD. When compared head to head, it showed that brentuximab improved the outcome of patients—not only their likelihood of staying in remission but their overall survival.
It was then compared as the standard to nivolumab, the PD-1-directed therapy, plus AVD chemotherapy in place of bleomycin. That then showed progression-free survival at a one-year follow-up. We don’t have mature data yet, but it seemed better already than the brentuximab-AVD chemotherapy and, as Dr. Grover touched on, less in the way of side effects and better tolerated.
That’s likely to become the new standard for advanced-stage patients. We want to see a little bit more mature data. But certainly, in elderly patients where toxicity is a real challenge, this has become a standard for many. We can see the progression from old-style chemotherapy to immune checkpoint plus chemotherapy as the front-line treatment.
Sam: These are exciting times. It’s wild because, for decades and decades, it seemed like we were doing the same thing for Hodgkin patients. Even if I were diagnosed with the same clinical scenario now compared to when I was first diagnosed in 2021, I would be treated differently.
There is still a subset of people where the disease proves to be very challenging and keeps relapsing… We still see patients who have gone through this standard treatment using these new drugs and then the disease comes back yet again.
Dr. Stephen Ansell
Gaps Clinical Trials are Filling
Sam: Can you tell us about these clinical trials and what gaps they fill?
Dr. Ansell: You heard us talk about two new drugs. They came from the relapsed setting but have moved up to front-line treatments. The gaps are for patients, heaven forbid, who have gone through these new therapies.
There is still a subset of people where the disease proves to be very challenging and keeps relapsing. That group’s getting to be smaller and smaller so that’s the good news. The challenging point is that it’s never good enough until there’s nobody in that group. We still see patients who have gone through this standard treatment using these new drugs and then the disease comes back yet again.
Things that are becoming exciting and that we need to do better on is what to do for those patients. Additional treatments that target these other immune checkpoints aside from PD-1 and other ways to make the immune system wake up and do its job are being tested.
The work that Dr. Grover and her team do is taking your immune cells, sending them to “training camp” to get a little docking site on them so they can detect the cancer in a much better way, and then unleashing them on the cancer. That’s proving exciting.
Finally, what we call bispecific antibodies. Those are also being tested and are some of the exciting opportunities in the future.
One arm of the antibody is directed to CD30, but the other arm grabs onto CD3 in the T cells.
Dr. Stephen Ansell
Bispecific Antibodies
Sam: Can you tell us about bispecific antibodies?
Dr. Ansell: This is an area that’s growing fast in Hodgkin lymphoma. Dr. Grover talked about CD30, which is on the cancer cells. One arm of the antibody is directed to CD30, but the other arm grabs onto CD3 in the T cells.
Bispecific antibodies bring those cells into very close proximity to each other. Like your kids in the back of the car who don’t like to sit next to each other and keep poking each other, this causes those cells to be grumpy with each other. The T cells, your immune cells, will then fight the cancer. That’s really what you want to see.
We talked about immune checkpoints that make T cells do a better job. One of the ways we’re doing that is on one arm, PD-1, which is an established immune checkpoint, but on the other, something like TIM-3, which is another immune checkpoint.
Other ways in which T cells are being switched off are now protected so it’s making those cells even more efficient. Those are two of the main ways bispecific antibodies are being tested right now.
With CAR T-cell therapy, we have seen some nice responses in patients whose disease has progressed after many different therapies, but there’s still work to do to improve these therapies.
Dr. Natalie Grover
CAR T-cell Therapy
Sam: Dr. Grover, how about CAR T-cell therapy and post-transplant relapses? Can you tell us about that and where CAR T-cell therapy might play a role?
Dr. Grover: As Dr. Ansell briefly mentioned, CAR T-cell therapy involves taking a patient’s T cells, sending them off, and re-engineering them so they can specifically target the CD30 protein on the cancer cell.
We have a CAR T-cell therapy trial at UNC and at the Baylor College of Medicine. There are two academic trials where we’re studying these CAR T cells in patients with Hodgkin lymphoma. There are also a few international trials. I know there’s a group in Spain and China.
Unfortunately, there isn’t a company-sponsored trial. They’re exciting treatments, but they’re not as easily accessible. Patients do need to travel for these for these treatments.
The big thing is long waiting lists, but we are hoping to get more patients treated more quickly because it still shows that there is an unmet need. Some patients have not responded, progressed after brentuximab, progressed after checkpoint inhibitors, progressed after transplant, and need additional options for treatment.
With CAR T-cell therapy, we have seen some nice responses in patients whose disease has progressed after many different therapies, but there’s still work to do to improve these therapies.
Right now, we have some patients who have been in remission for many years—five-plus years after getting CAR T cells. Many patients get the CAR T cells and have a great response, but their disease relapses afterward. We’re trying to figure out why that’s happening and how we can improve the CAR T cells and improve outcomes for patients.
Patients who relapse can have more aggressive disease as opposed to some other more aggressive types of lymphoma, but with Hodgkin, patients who have relapsed oftentimes can live a long time even with the disease.
Dr. Natalie Grover
Dr. Ansell: There’s one other option that takes both bispecifics and cellular therapies and combines those strategies. That’s taking the natural killer cells from cord blood and using a bispecific antibody that targets CD30 and a protein called CD16 on the NK cell. It sticks this bispecific antibody to the NK cell.
They pre-treat the NK cells before they give them to the patient and then infuse them. You activate the cells outside the body, add the bispecific antibody so that it’s already stuck to the NK cells, and infuse them. Those also have been effective therapies.
Dr. Grover’s right. We’re still learning about how many treatments you need to get. They’re getting high response rates, but the durability is still in question. But I think that’s another exciting strategy of taking cellular therapies and bispecifics and using them together.
Dr. Grover: I think that’s the LuminICE trial, which will be open at several different sites across the country.
Sam: That’s great. That’s an important point. It’s part of the issue of Hodgkin lymphoma compared to non-Hodgkin’s. It’s not nearly as common in terms of the number of people that will qualify for these trials so that may be why there are less commonly offered.
Dr. Grover: Hodgkin lymphoma has higher cure rates and is less common. A lot of times, patients who relapse can have more aggressive disease as opposed to some other more aggressive types of lymphoma, but with Hodgkin, patients who have relapsed oftentimes can live a long time even with the disease.
I’ve seen patients in my trials who have relapsed and have not even been in remission but have been living for many, many years with relapsed disease. A lot of times, these patients may not be as sick, which is a good thing, so they’re able to travel and participate in these trials. Many of these patients may be alive and doing well even though they’re going through treatment or have some disease left.
An allogeneic transplant is still a curative option and something that we would always consider.
Dr. Stephen Ansell
Transplant
Sam: Where is all this in relation to allogeneic transplants for people who are relapsing after transplant? Allogeneic, meaning the donor is somebody else, as opposed to autologous, which is more common in Hodgkin.
Dr. Ansell: To be honest, an allogeneic transplant is still a curative option and something that we would always consider. It’s a little bit high-risk because of the potential for longer-term toxicities.
With a lot of these novel treatments, many of which have been very successful in the past, people delayed allogeneic transplants a little bit. There are some challenges now as patients are having their disease come back after standard treatment so there is a subset of patients for whom that needs to be considered. That’s a very individualized discussion between patients and their doctors to weigh the risks versus the benefits.
One of the key questions to ask is what treatment somebody got as their first line because that impacts what you would do in the second line.
Dr. Stephen Ansell
Developments in Salvage Therapy
Sam: Dr. Ansell, what are some of the developments in salvage therapy, which is given when somebody has their initial relapse?
Dr. Ansell: It’s moving pretty fast right now. Novel drugs are being used in the front line so one of the key questions to ask is what treatment somebody got as their first line because that impacts what you would do in the second line.
However, based on where most patients are right now, not very many have had an immune checkpoint treatment, which is the nivolumab and pembrolizumab that Dr. Grover spoke about. Not too many people have had that as their front-line treatment and using those in combination with standard chemotherapies, like ICE chemotherapy or GVD chemotherapy. In the majority of particularly younger patients, going to more intensive treatment and a stem cell transplant using your own cells is very much the standard management.
Some interesting recent data compared where that was used to standard chemotherapy or the use of brentuximab and chemotherapy then a transplant and then looked at outcomes. The patients with the best outcome got a PD-1 antibody before they got their transplant.
Dr. Grover touched on this, which is an important point. The PD-1 blocking antibody team seems to change the immune system a bit and make patients more sensitive to some of the chemotherapies after the fact so that’s why it seems like it makes a difference. We tend to favor chemotherapy with immune checkpoint therapy as a treatment approach before going to transplant.
We want to see people cured. Heaven forbid that it comes back the first time, but if it does, all the gloves are off. Now we’re going at it as hard as we possibly can.
Dr. Stephen Ansell
Sam: That’s interesting because I know in other cancers, people will save therapies or not want to expose them because the body will learn them. What you’re saying is that the same principle may not apply in Hodgkin. These therapies may sensitize to other therapies or make people respond better so you don’t necessarily need to leave them until later when you’ve burned through other options.
Dr. Ansell: Correct. We want to see people cured. Heaven forbid that it comes back the first time, but if it does, all the gloves are off. Now we’re going at it as hard as we possibly can and we want to utilize all the effective tools that we have so that we can truly beat it into the ground. That’s what I would recommend. Different from other cancers where you might want to string things along in a palliative approach. With Hodgkin, you want to go after it with curative intent.
Sam: It’s wild to think how quickly things evolve and how important it is for patients to seek out providers or treatment at cancer centers who have some connection with the trials and know the latest updates.
How can we advise patients to seek out that kind of care? How can they ask for that from their oncologist if they’re getting treatment in the community?
Dr. Ansell: Be an informed patient. Ask questions and be a strong advocate for yourself. There are excellent resources, like The Leukemia & Lymphoma Society, which have good information related to many of these topics. Being informed about the best way to be managed is useful.
When your doctor sees you and goes through things, asking questions relative to the information that you have helps you feel reassured that you’re on the right track. Most of us are quite okay with patients getting second opinions from other colleagues.
Second opinions help people reinforce the messages you’re already giving. People will be more comfortable doing what needs to be done if they’re hearing the same thing from more than one person. All of that pertains to a good outcome. If you ask questions, make sure you get your questions answered.
Sam: Thanks for empowering patients because it’s so hard to make these decisions even when you have a lot of resources and education. It could be such an emotional time, in addition to not feeling well, and it’s helpful to hear that you expect people to want other opinions and be informed.
Dr. Ansell: To be honest, a lot of patients come in and get so much information that it’s pretty challenging to retain them. I always tell people to bring friends or family. Have other sets of ears that can help reinforce some of the messages so that when your brain is locked down and you can’t think straight, they hear things that you might have missed.
The treatments are getting better all the time so there’s a lot of hope. I’m hoping that in the not-very-distant future, every patient with Hodgkin lymphoma can be cured with front-line treatment.
Dr. Stephen Ansell
Final Messages
Sam: Dr. Grover, can you give us some final points or takeaway messages?
Dr. Grover: I’m excited about improving earlier therapies and moving these newer therapies to the front line both to hopefully enhance cure to prevent patients from relapsing again and reduce long-term toxicities and improve quality of life.
There’s still an unmet need for patients who are refractory to PD-1 inhibitors, brentuximab, and chemotherapy. I’m hoping that over the next few years, we will have more clinical trials and more developments for that patient population.
For patients, ask questions of your provider. Don’t be shy about getting a second opinion. I’m never offended if a patient goes for a second opinion.
Sam: How about you, Dr. Ansell?
Dr. Ansell: If you’re a patient with Hodgkin lymphoma, there are unique and novel treatments that are making a big difference to patient outcomes. The treatments are getting better all the time so there’s a lot of hope. I’m hoping that in the not-very-distant future, every patient with Hodgkin lymphoma can be cured with front-line treatment.
Sam: Thank you so much for that. I remember initially being scared about death and dying. I think that’s what a lot of people think about when they hear the word cancer. Once it began to move away from that and began to become living with cancer or living life after a cancer diagnosis, I thought, I’d like to jog, paint, play guitar, hold my kids, and be able to think as well as possible.
These trials to improve quality of life while simultaneously improving outcomes are so meaningful personally. I know it means a lot to our patient population that you took the time to have this conversation with us. Thank you so much.
Dr. Ansell: My pleasure.
Dr. Grover: Thanks so much for having us.
Stephanie: Thank you so much, Sam, for being our incredible patient advocate and moderator. Also, thank you to Dr. Grover and Dr. Ansell, for the work and research you do to help move the landscape of treatment options in Hodgkin lymphoma.
We hope that you walk away with a better understanding of the latest treatments and clinical trials in Hodgkin lymphoma. They may or may not be right for you, but our goal is to make sure you feel empowered to make a decision for yourself.
Thank you and we hope to see you again at a future program at The Patient Story.
Special thanks again to Pfizer for its support of our independent patient education content. The Patient Story retains full editorial control.
This interview has been edited for clarity and length. This is not medical advice. Please consult with your healthcare provider for treatment decisions.
Interested in myelofibrosis clinical trials? We’ve gathered the leading experts to explain emerging clinical trials, misconceptions, and how to find the treatment best for you.
Gain invaluable insights into upcoming exciting clinical trials, the purpose and benefit of trials, and navigating trials and treatments. Optimize communication with your healthcare team and empower yourself with extra support and resources.
Thank you to GSK for its support of our patient education program! The Patient Story retains full editorial control over all content.
This interview has been edited for clarity and length. This is not medical advice. Please consult with your healthcare provider for treatment decisions.
We try to help patients and their supporters navigate a diagnosis and we do this through in-depth conversations with patients, care partners, and top specialists across different cancers.
It’s important to have these educational programs, especially when it comes to topics like clinical trials, which are daunting and overwhelming, so we’re trying to humanize your options.
We’re so proud to be co-hosting this with The Leukemia & Lymphoma Society, the world’s largest non-profit health organization dedicated to funding blood cancer research as well as offering patient services and education.
They have great resources, including information specialists who are a phone call away to help answer your questions. We’ll be highlighting the Clinical Trial Support Center, a very critical free resource that offers one-on-one support to enroll in and stay in clinical trials.
We also want to say special thanks to GSK for supporting our educational program, which helps us make this available and free for our audience. The Leukemia & Lymphoma Society and The Patient Story retain full editorial control of the entire program.
This is not meant to be a substitute for medical advice. We want you to walk away and be able to ask your own doctors and medical teams questions about clinical trials in myelofibrosis.
I know how fortunate I am as many people suffer so much more than I ever have.
Ruth Fein Revell
Ruth Fein Revell, Patient Advocate
Stephanie: I’m thrilled to introduce someone who’s not only a big MPN and myelofibrosis patient voice and leader in the community but also someone I’m lucky to call a friend and who will be leading the conversation.
Ruth, I know that you’re going to share more about your own myelofibrosis cancer story and how you became a passionate advocate. But first, can you share more about yourself outside the cancer context? Because as we know, we are so much more than a diagnosis.
Ruth Fein Revell: Thanks so much, Stephanie. Professionally, I’m a health and science writer who now writes primarily about cancers, blood cancers in particular. I also host patient programs. I have the privilege of speaking to many of the world’s most prominent researchers and clinicians.
In many ways, I think cancer has attracted many of us because we feel we can make a real difference in a difficult disease.
He’s globally recognized as a leader in the MPN space and we are so fortunate to have him with us. Our audience would love to know you beyond that white coat of yours. What drew you to work in cancer and research?
Dr. Ruben Mesa: Cancer is such a terrible disease. It impacts and steals from an individual’s length of life and quality of life. I myself have been touched by cancer as so many have. My father passed from cancer and my mother is a cancer survivor. I was able to witness the impact of cancer research, developing new therapies, and the value of really compassionate care and how important these things were.
In many ways, I think cancer has attracted many of us because we feel we can make a real difference in a difficult disease. It’s also an exciting time when scientific progress is really making a genuine impact.
There are many aspects of myeloproliferative neoplasm that I find extremely rewarding to take part in.
Dr. Angela Fleischman
Dr. Angela Fleischman, Hematologist-Oncologist
Ruth: Dr. Angela Fleischman is a hematologist-oncologist at UC Irvine Health, where she leads the Fleishman Lab with a special focus on MPNs and improving the options and care for patients.
As a physician-scientist, Dr. Fleischman not only treats patients but also actively researches hematological malignancies. She’s passionate about translating findings from the lab bench to the patient’s bedside.
Dr. Fleischman, we’d love to know a little more about your passions as well. What drew you to blood cancers and research?
Dr. Angela Fleischman: I have always been extremely interested in blood cell development. I started out as a Ph.D. student prior to my MD and focused on normal blood cell development and what determines whether a blood stem cell goes one direction or the other.
When I decided to go to medical school and first learned about myeloproliferative neoplasms, I was extremely fascinated by them because I felt that it was an opportunity to learn what happens when blood cell development goes awry.
Another extremely interesting aspect of myeloproliferative neoplasm that I was extremely drawn to is the ability to make connections with patients throughout the years because it’s a chronic disease. As a physician, I’m able to travel with them through their journey as a patient. There are many aspects of myeloproliferative neoplasm that I find extremely rewarding to take part in.
I help patients navigate the complicated clinical trial landscape, and provide them with education and potential treatment options to take back to their care team.
Melissa Melendez: I’ve been in the oncology field for almost 20 years and it was a happy accident how it happened. While in nursing school, I started my first clinical rotation in the oncology unit. I was pretty apprehensive and concerned that I was being plunged into caring for such complex patients with extreme highs and extreme lows of treatment outcomes.
I instantly fell in love with not only helping patients on their journeys throughout their treatment but also the privilege of caring for their families who were going through the journey as well. I decided that oncology was going to be my career path.
I started as a patient care assistant then a registered nurse, a division supervisor, and currently a nurse practitioner. Working for The Leukemia & Lymphoma Society in the Clinical Trial Support Center has been such a blessing for me as a nurse and it was a pretty easy transition from my previous occupation.
I help patients with clinical trials and throughout their journey. Not only do I work with intelligent, caring, and selfless colleagues but also with a population of patients and families that I truly love.
On a daily basis, I get to see the impact that the LLS has on patients and families, help patients navigate the complicated clinical trial landscape, and provide them with education and potential treatment options to take back to their care team to discuss so they can make informed decisions about their care. I get to build relationships with patients and family members that last for years.
It wasn’t until I was taken off hydroxyurea before starting a clinical trial that I realized how severe my symptoms were without treatment.
Ruth Fein Revell
Ruth’s MPN Story
Ruth: What is myelofibrosis? Myelofibrosis is one of the MPNs, a myeloproliferative neoplasm, and a very personal topic for me. I’ve lived with an MPN for nearly 30 years, originally diagnosed with essential thrombocythemia or ET at age 38 while I was raising two young boys.
I was taking an aspirin a day, which was stopped because I developed an ulcer. I ended up with clots in my portal and splenic veins. After a week in the hospital, I was put on an anticoagulant or a blood thinner. Several years later, my bone marrow flipped a proverbial switch and instead of producing too many platelets, it now produced too many red blood cells.
The diagnosis was changed to polycythemia vera and I lived with periodic phlebotomies and daily hydroxyurea. That was part of my life, as with many people who live with polycythemia vera and the different MPNs.
In 2018, I had surgery for early colon cancer. The surgeon was so focused on avoiding any more clots that I had the opposite happen. A major bleeding episode put me in the ICU for nearly a week, followed by several months of healing.
I finally sought out an MPN specialist and began to see Dr. Ellen Ritchie at Weill Cornell in New York. I had an updated bone marrow biopsy, which confirmed a diagnosis of myelofibrosis.
I used to say I was mostly asymptomatic but I’ve lived with severe migraines, a few TIAs (transient ischemic attacks), and other constitutional symptoms my whole life. It wasn’t until I was taken off hydroxyurea before starting a clinical trial that I realized how severe my symptoms were without treatment.
I experienced both life-threatening clots and bleeding episodes. I had such extreme fatigue that I couldn’t walk up the street without stopping to lean or sit on a neighbor’s step. Of course, I also know how fortunate I am as many people suffer so much more than I ever have.
Fibrosis does not always equal the MPN myelofibrosis.
Dr. Angela Fleischman
What is Myelofibrosis?
Ruth: Let’s dig right in. Dr. Fleischman, what exactly is myelofibrosis?
Dr. Fleischman: People may interpret the word myelofibrosis as having some fibrosis in the bone marrow. What we’re talking about is the myeloproliferative neoplasm myelofibrosis, which also can have some fibrosis in the bone marrow. However, I want to emphasize that fibrosis in the bone marrow does not always equal myelofibrosis.
MPN myelofibrosis is a chronic blood cancer that stems from the proliferation of some abnormal mutant cells in the bone marrow. Exactly what causes the fibrosis is unclear. The abnormal megakaryocytes or the cells that are producing platelets have been implicated as the bad cells in myelofibrosis and causing the fibrosis.
Patients also tend to have an enlarged spleen, which can also be seen in ET and PV but is more prevalent in myelofibrosis.
Blood counts can look very different. There’s a wide variety of what a myelofibrosis patient’s blood counts look like, but a classic myelofibrosis patient may have some anemia. They may have a little bit of a high white blood cell count. They may also have immature cells in their blood so their bone marrow cells are not maturing fully before going into the blood, indicating that there’s some stress going on in the bone marrow.
Myelofibrosis patients can have some significant constitutional symptoms. ET and PV can also, but in myelofibrosis, they tend to be more severe.
I do want to emphasize that because somebody has a bone marrow biopsy that says fibrosis does not necessarily always equal the MPN myelofibrosis. Other things, like autoimmune diseases, can cause some fibrosis in the marrow. Infections can cause fibrosis in the marrow. Other blood cancers can cause fibrosis in the marrow. What I want to emphasize is fibrosis does not always equal the MPN myelofibrosis.
Ruth: That’s a really good reminder and not something that people focus on much so thank you for that.
We’ve seen an explosion in many different types of therapies. Over the last three years, we’ve seen a rapid increase in FDA-approved options.
Dr. Ruben Mesa
Advances in Myelofibrosis Treatments
Ruth: The world of MPNs, in particular myelofibrosis, is changing before our eyes as clinicians, researchers, and people living with these conditions. Dr. Mesa, would you tell us how the landscape of treatments for MF patients has changed so dramatically in the last 2 to 3 years?
Dr. Mesa: I first saw patients with myelofibrosis at the beginning of my training almost 30 years ago. In the first half of those 30 years, the medicines we had for myelofibrosis were really limited because we had a very limited understanding of the biology of the disease.
What happened about 15 years ago is we identified important genetic changes, such as JAK2, CALR (calreticulin), MPL, and others that lead downstream to a patient having a myeloproliferative neoplasm.
With that, we’ve seen an explosion in many different types of therapies. Over the last three years, we’ve seen a rapid increase in FDA-approved options, now four different JAK2 inhibitors. They’ve made a real impact in patients with myelofibrosis regarding the enlargement of the spleen, perhaps helping to slow down the course of the disease to some degree and, for some individuals, dramatically so.
The next step we’re launching into is combinations of therapies where we use more than one drug and look at treating different aspects of the disease or different targets in terms of the biology of the disease to make a deeper impact.
Wearing my cancer center hat, as I look at how therapies are advancing in many different diseases, both blood cancers as well as non-blood cancers, most of the time we’re now using more than one therapy where medicines complement each other.
Different blood diseases, such as multiple myeloma, use up to four different drugs at a time. The explosion went from really very little understanding to multiple drugs, a much greater understanding of the biology of the disease, and hopefully a deeper and deeper impact.
For the majority of individuals, probably over 90%, based on a variety of factors, we start with medicines.
Dr. Ruben Mesa
Standard of Care: First-Line Treatment
Ruth: Dr. Mesa, what is the standard first-line treatment for myelofibrosis?
Dr. Mesa: When patients come in with a diagnosis of myelofibrosis, their doctor first gets a sense of the risk of the disease, how likely is the disease to be life-threatening, and the burden that the patient is facing from an enlarged spleen, from symptoms, or from the risk of progression.
We discuss whether we should pursue the potentially curative option of bone marrow transplant or stem cell transplant; we use those terms interchangeably. That’s a very complex therapy, but it’s something that we consider throughout for individuals up until their 70s, depending on the risk of the disease and other factors.
For the majority of individuals, probably over 90%, based on a variety of factors, we start with medicines. The only approved medicines for myelofibrosis are the JAK inhibitors. Transplant either in the near future, delayed, or we’re not going to pursue transplant and then consideration of a JAK inhibitor.
JAK inhibitors help to decrease the activation of JAK2. Regardless of which mutation a patient has or even if they don’t have one of the three mutations, they all seem to benefit from JAK inhibitors.
Dr. Ruben Mesa
How JAK Inhibitors Work
Ruth: We currently have four FDA-approved JAK inhibitors, including momelotinib, which was approved in September 2023. How do JAK inhibitors work? For each of the approved JAK inhibitors, would you explain what their benefits and limitations are?
Dr. Mesa: In myelofibrosis, there are three main mutations that we believe are involved with causing the disease. The JAK2 or the JAK2 V617F, the mutation in calreticulin, and the mutation in MPL. There’s even a small subset of people who do not have one of those three.
All of those mutations lead to the same outcome: an overactivation of the protein JAK2. JAK2 is one step. It’s an on-off switch stuck in the on position telling cells to grow.
JAK inhibitors help to decrease the activation of JAK2. Regardless of which of those mutations a patient has or even if they don’t have one of those three mutations, they all seem to benefit from JAK inhibitors.
Ruxolitinib has been approved since 2011. It improves the spleen and symptoms, may help patients who respond live longer with the disease, and in many ways has long been the standard. It’s frequently been used as the base in combination trials.
Fedratinib has been approved since 2019. It can be used to improve the spleen or symptoms. It may be used in the front-line setting instead of ruxolitinib or in the second-line setting if someone has had ruxolitinib already.
Pacritinib was approved in 2022 and this one has a little distinct profile. It’s particularly helpful for decreasing the spleen and symptoms but for individuals with a very low platelet count.
Both ruxolitinib and fedratinib are approved for individuals with a platelet count above 50,000. Pacritinib can be helpful in anyone, but its particularly unique niche is in individuals under 50,000 and we certainly will consider it for individuals with lower blood counts.
Momelotinib was approved in September 2023. This can improve the spleen symptoms and anemia. It showed the strongest improvement in anemia compared to the other three. Pacritinib sometimes can have an improvement in anemia. Unfortunately, both fedratinib and ruxolitinib sometimes can have anemia as a side effect or worsen anemia and rarely would improve anemia.
There are some differences among the four of them, but they overlap in many ways in terms of improving the spleen and symptoms and can be beneficial regardless of the mutation profile that a patient with myelofibrosis has.
Ruth: It’s very exciting for the MPN community to finally have so many treatment options. People often think that because they have mutations other than JAK2, a JAK inhibitor won’t help them so thanks for noting that that’s not necessarily the case.
It’s really exciting now that we have four different JAK inhibitors so we can try to tailor the best JAK inhibitor for the person upfront.
Dr. Angela Fleischman
Navigating Treatment Options
Ruth: Dr. Fleischman, here’s a loaded question. How do you know which JAK inhibitor may or may not work and which one to try first?
Dr. Fleischman: This is an evolving topic. It’s really exciting now that we have four different JAK inhibitors so we can try to tailor the best JAK inhibitor for the person upfront. Sometimes it’s a hit or miss but, as Dr. Mesa described, each JAK inhibitor has a little bit of a different profile.
All of the JAK inhibitors inhibit JAK2 but each one has “off-target” effects and some different proteins and that may explain why they have their own unique profile.
Each myelofibrosis patient is quite unique so they have different needs. For example, for somebody who has an enlarged spleen, with symptoms, and pretty robust blood counts, ruxolitinib would be a great option, which is also the only JAK inhibitor currently approved for PV, in which the purpose is to bring down blood counts.
If the person’s primary problem is anemia, which is unfortunately a very common problem in myelofibrosis, it’s very exciting that we have an option that’s specifically designed for patients with anemia. That’s a patient population very, very appropriate to start pacritinib first.
Many patients with anemia also have a low platelet count. What do you do for somebody who has both anemia and a very low platelet count? We’re going to have to learn how to sequence and make decisions between pacritinib and momelotinib. For a myelofibrosis patient with both anemia and thrombocytopenia or low platelet count, the two options that exist upfront are momelotinib and pacritinib.
Different tiers of needs as we talk about individual clinical trials.
Dr. Ruben Mesa
Combination Therapy Clinical Trials
Ruth: Some of the most exciting clinical trials for MF patients are for combination therapies. Dr. Mesa, can you explain the idea behind combination drug approaches and who might benefit?
Dr. Mesa: We think about different populations of patients. We have those who are JAK inhibitor naive or individuals who have not had a JAK inhibitor yet. This may be at the time of diagnosis or individuals who have had the disease for a while, have been observed, and now, based on spleen symptoms or changes, need to begin therapy.
There are individuals who have been on a JAK inhibitor and have had some benefit, but we feel that there’s an opportunity for further benefit. Some of these individuals are participating in add-on studies where you have a JAK inhibitor that they’ve been on for a while, they have a partial response, and a second drug is added.
The third type of patient is an individual who was on a JAK inhibitor and now no longer has a benefit from that medication so you are switching them to a different therapy altogether. Different tiers of needs as we talk about individual clinical trials.
Selinexor + JAK Inhibitor
Ruth: Let’s talk about some of those combination trials. There are a number of them where JAK inhibitors are given with the addition of a new agent with a different mechanism of action. Let’s talk about selinexor plus JAK inhibitor.
Dr. Mesa: There’s a whole constellation of different agents that have an impact on different mechanisms of action that are being looked at in combination with JAK inhibitors. This one is a little bit earlier in its development.
It’s an approved drug for multiple myeloma and has been approved since July 2019. It’s an anti-cancer medication. It’s a selective inhibitor of nuclear export. It works on some of the processes within the cell in a different way that we feel may be beneficial in combination.
Data from early studies suggest that there is benefit and it may be more with two drugs than the single drug itself. Whether this will become an option for patients with myelofibrosis, the trials will demonstrate, but it has made an important impact for individuals with myeloma so we’re hopeful that it’ll be helpful in this group of patients as well.
Ruth: It’s great to see when we borrow from different areas of research.
Navitoclax + JAK Inhibitor
Dr. Mesa: This works against a process within cells called apoptosis or programmed cell death. Navitoclax is a cousin of a drug that’s approved for acute leukemia called venetoclax.
In studies with myelofibrosis, navitoclax has shown real activity for decreasing spleen symptoms and potentially impacting the disease and, in combination, to a greater degree than JAK inhibitor alone. We have had patients on large phase 3 trials who have been newly diagnosed as well as other situations so those data are anticipated with great interest.
It may take further time for us to identify which combination is a better fit for a patient. These trials are not necessarily designed to answer that itself.
Dr. Ruben Mesa
Pelabresib + JAK Inhibitor
Ruth: Let’s talk about pelabresib, a drug very close to my heart. That’s the trial I’ve been on for more than three and a half years used in combination with a JAK inhibitor. I understand the results have been very promising. At Weill Cornell, they’re calling me the poster child for this study so I’m very grateful for that. Dr. Mesa, tell us about the MANIFEST-2 trial.
Dr. Mesa: This is probably the furthest along of the combination approaches. Pelabresib is an inhibitor of another cellular process called BET. There’s reason to believe that it may have a very complementary role in inhibiting JAK2.
In the early studies, it appeared very promising in terms of having an impact, perhaps more than JAK inhibition alone or in combination when individuals had failed a JAK inhibitor.
We now have phase 3 trials of patients newly diagnosed or who are JAK inhibitor naive receiving this combination versus ruxolitinib alone. We are looking for information to see the net benefit of using the two drugs.
Are the responses more profound? Do they last longer? Are patients better off? We always weigh any downsides to being on two drugs versus one. There are multiple combinations being tested in parallel. It’s possible that multiple of them may be beneficial. It’s possible that multiple of them could become FDA-approved.
It may take further time for us to identify which combination is a better fit for a patient. These trials are not necessarily designed to answer that itself. They’re designed to answer if they are better than a JAK inhibitor alone.
Downstream, we’ll have a better understanding based on specific patient features or other aspects of their health whether one of these combinations may be a better choice for one patient versus the other.
Ruth: Dr. Fleischman, what should patients be asking their doctors to understand if one of these combination therapies might be best for them?
Dr. Fleischman: Entering into a clinical trial is a personal decision for the patient and deserves deep thought. There are many reasons why somebody may want to do a combination therapy. It’s not only because your current therapy isn’t working or that you want something “new” but also to help other people.
Clinical trials are not necessarily only supposed to be for the benefit of the patient themselves, but by participating in a clinical trial, the patient is increasing our knowledge of whether specific combinations work, the appropriate dosing, and the side effects. You’re helping other patients who will come after you.
Cancers are pretty smart that if you target one, they’re going to find a way to get themselves around that medicine you’re giving them.
Dr. Angela Fleischman
Trials Beyond JAK Inhibitors
Ruth: We go into clinical trials often because we were on Jakafi or another treatment and it wasn’t effective, caused side effects that were serious and needed to be discontinued, or maybe it worked for some time and then stopped. Dr. Fleischman, can you talk more about aiming to introduce non-JAK inhibitor treatments?
Dr. Fleischman: JAK inhibitors are very good in terms of reducing inflammation and reducing spleen size and, in some patients, can work very well for a period of time.
Patients could get “resistance.” Resistance with JAK inhibitors is very different than what we think about with other cancers. People on JAK inhibitors don’t develop new mutations that make them “resistant” to the JAK inhibitor. They start to not work as well so that would be one reason to add on and target different pathways.
Myelofibrosis is very heterogeneous. Each patient is very different. Each patient may have different mutations. They may have either JAK2, calreticulin, or MPL, but some patients will have additional mutations that make them look a little bit different than other myelofibrosis patients.
Trying to target multiple pathways, as Dr. Mesa had mentioned, is a very common technique. Cancers are pretty smart that if you target one, they’re going to find a way to get themselves around that medicine you’re giving them. They’re quite ingenious and able to grow despite our single treatments. Each myelofibrosis patient is very different so identifying what the appropriate second agent would be is really on a case-to-case basis.
Part of the challenge that we have with medicines against blood cancers or cancers is finding ways to deliver medicines solely to the cells affected by the disease without harming normal cells.
Dr. Ruben Mesa
Ruth: What’s exciting to see is that we’re more forward-thinking in our endpoints of clinical trials so we’re looking more at survival and not just symptom relief.
All of the clinical trials that we’ve talked about so far are exploring new drug treatments. There are also trials that look at lifestyle issues like exercise or the benefits of yoga and meditation.
Dr. Fleischman is renowned for her work studying inflammation and diet. She and her collaborators recently published the results of a clinical trial that tested the feasibility of the Mediterranean diet for MPN patients.
For those of us living with an MPN, anything we can do ourselves to potentially control our symptoms is very welcome. In fact, it helps us feel in control of our own blood disorder. Even if it’s only a little bit, it’s important.
Dr. Mesa, let’s move on to an area of treatment that the MPN community is very excited about exploring, which is a novel therapy targeting calreticulin, the CALR mutation, one of the most common drivers of essential thrombocythemia and myelofibrosis. People are calling this a potential vaccine. What can you tell us about this that explains it best?
Dr. Mesa: About a third or more of patients with myelofibrosis have a mutation in the protein called calreticulin. This is a little different from JAK2 and MPL because calreticulin might be on the surface of the affected cells and we may be able to target the abnormal calreticulin in a specific way.
Part of the challenge that we have with medicines against blood cancers or cancers is finding ways to deliver medicines solely to the cells affected by the disease without harming normal cells. In the bone marrow, that’s particularly important.
There has been a great interest in seeing if we can target calreticulin in a specific way. A vaccine trial has been done in Europe and is in its infancy.
There’s a theme of multiple different approaches being developed, both cellular-based therapies, such as CAR T or vaccines, or a monoclonal antibody against calreticulin. That is creating great interest but has not yet started in human trials. In the laboratory, it appears to be a very promising medicine.
We’re very hopeful, but we also recognize that until we’ve started treating patients, we never know how good a fit it’s going to be, if there’s going to be an unexpected side effect, or if it will have the benefit that we hope that it has.
I certainly hope that this medication is successful. Even if it is not, I suspect there will be others behind it that hopefully will be. We learn from trials whether they end up being a home run or not. This theme of us trying to selectively target the cells involved is really key.
As we think about anemia, there are JAK inhibitors that can have an impact on the spleen and symptoms, but they may either worsen anemia or not improve anemia.
Dr. Ruben Mesa
Treatment for Patients Who Suffer From Anemia
Ruth: Dr. Mesa, as we know, anemia is very common in myelofibrosis and many people need regular transfusions so this isn’t something that’s likely to go unnoticed. There can be severe fatigue associated and MF patients will have regular blood tests so in theory, it should be seen and diagnosed early on. Tell us about some of the new hopeful treatment options for MF patients who suffer from anemia.
Dr. Mesa: Anemia is when an individual has fewer red blood cells than they’re supposed to. Red blood cells carry oxygen from our lungs to the rest of the body so that’s key for us in terms of our muscles to work well and for us to feel well. That’s why we can have issues in terms of anemia.
Myelofibrosis anemia has multiple aspects. There can be baseline anemia because the bone marrow is not producing enough red blood cells. There can be other contributors if they’ve had baseline iron deficiency that contributes to that. If the spleen is very enlarged, it can hold on to many red blood cells.
Historically, we’ve had a range of options. None of them have been overly dramatic in terms of their impact, but they can help. Injections such as erythropoietin-stimulating agents and androgens like testosterone help to produce red blood cells in both men and women.
There are medicines that are in development. Luspatercept, a medicine that can help with anemia, is currently in phase 3 clinical trials for patients with myelofibrosis. Momelotinib, which was most recently in September 2023, is a JAK inhibitor that can also help to improve anemia.
We look for that medicine to improve both spleen symptoms and anemia. As we think about anemia, there are JAK inhibitors that can have an impact on the spleen and symptoms, but they may either worsen anemia or not improve anemia. Both things can be present.
Momelotinib is an important advance. I hope that as we see other combination therapies, we may see broader improvement in spleen symptoms and anemia.
Should momelotinib or those agents that are more helpful with anemia, perhaps even pacritinib, be that JAK inhibitor to be used with other medications in combination? That has yet to be answered with some of these combinations.
Some real progress in anemia and improving anemia can clearly have a benefit, in terms of the patient’s quality of life and their ability to have enough energy to do their daily activities or things they enjoy, as well as being easier on the body.
One area that we’re intensely working on is trying to identify surrogates for survival or something that we can capture with data amenable to a clinical trial that will be a marker for disease impact.
Dr. Angela Fleischman
Symptom Control While Being on Treatment
Ruth: Dr. Fleischman, what I find very exciting in today’s clinical trials is that we’re moving beyond symptom management and moving more toward progression-free survival, living longer with a high quality of life. When evaluating clinical trials, it’s important to understand the goal of the study. Where do you think we are with this?
Dr. Fleischman: That’s a very important point. For a clinical trial, you need to have an endpoint, a defined thing that you’re going to test. Ideally, something that you anticipate that your drug of interest is going to achieve better than the comparator.
Classically, in myelofibrosis, we’ve focused on spleen volume reduction and symptom burden because those are two things that we can quantify and expect to see a change in a short period of time. Although spleen size reduction and symptom burden are extremely important, they just don’t capture the whole picture of myelofibrosis.
The endpoint of survival obviously is extremely important to myelofibrosis patients. Survival is extremely important to everybody. But because, in general, myelofibrosis patients live a long time, it’s not a feasible outcome for clinical trials.
One area that we’re intensely working on is trying to identify surrogates for survival or something that we can capture with data amenable to a clinical trial that will be a marker for disease impact.
There are some clinical trials such as the imetelstat clinical trial in which survival is the actual endpoint, which is a unique and forward-thinking endpoint. One of the key areas of need in myelofibrosis is identifying markers that can be used in clinical trials that indicate a significant impact on the disease that goes beyond reducing spleen size and symptoms.
Ruth: We’re definitely getting into a very exciting time that will make such a difference therapeutically once we have those answers.
A transplant itself is an extremely risky procedure that can lead to significant side effects or even death.
Dr. Angela Fleischman
The Best Time to Get a Stem Cell Transplant
Ruth: When is the best time to get a stem cell transplant? I know there isn’t a black-and-white answer, but Dr. Fleischman, how do you answer this common question?
Dr. Fleischman: That is another million-dollar question in myelofibrosis and I think the most difficult decision for a myelofibrosis patient as well as for the physician.
As we know, at this point in time, a bone marrow transplant is the only curative option for patients with myelofibrosis. You may say, “If it’s curative, why doesn’t everybody just get a transplant?”
Transplants themselves can be quite risky. The media may miscommunicate transplants. You always see on the news that somebody’s looking for a donor so it may seem that the only problem with transplants is you can’t find a donor. That’s not necessarily the case.
A transplant itself is an extremely risky procedure that can lead to significant side effects or even death. We don’t want to give somebody a transplant if the transplant is going to make them sicker or potentially lead to their death earlier than would be the case if they just treated their myelofibrosis through other means.
The ideal time to transplant is when you get clues from this myelofibrosis patient that with standard treatments, they are very likely going to have an extremely bad outcome or will have an outcome that will lead to their death very quickly. That’s the time going forward with a transplant is worth the significant risk.
The safer the transplant becomes, the greater the consideration of when it is used.
Dr. Ruben Mesa
Dr. Mesa: There is a balance between a patient undergoing a stem cell transplant and a medical treatment. They have very different dynamics. A stem cell transplant can potentially be curative but can come with significant risks, including upfront risk.
The benefits of medication depend on many things, like how much benefit, how long is that benefit, and the impact on the patient. I would certainly view it as a success if we are able to have medicines that are sufficiently impactful that it leads us to either be able to skip a bone marrow transplant or delay it further.
We have precedent in other areas and the most successful example is in chronic myeloid leukemia. At the beginning of my career, most young patients had a stem cell transplant. Now, with the impact of medications, it is rare for patients to have a stem cell transplant because of the effectiveness of medications.
Currently, we are not there yet. A patient who clearly needs a transplant still will go for a transplant. Over time, there may be more combinations of both. Can the medicines help to decrease the burden of the disease and make the likelihood of success with the stem cell transplant greater? That is also a win.
In parallel, there’s tremendous research from our colleagues who do stem cell transplants to try to make that process safer. The safer the transplant becomes, the greater the consideration of when it is used.
It continues to evolve. We reevaluate every option we have. Does that change the dynamic in terms of transplantation as well as how the two things work together? With our current medicines, we are not changing our decisions for transplant, but increasingly, almost all patients that go to transplant have had at least one or more of the JAK inhibitors ahead of time.
The data would suggest that the outcomes with transplant are better in part because of JAK inhibitors but also because of improvements in the processes, antibiotics, other medications, and expertise of our colleagues who run transplant centers.
Asking About Clinical Trials
Ruth: When should a patient ask about clinical trials? How and when do you introduce the idea of considering a clinical trial to your patients?
Dr. Mesa: Clinical trials may exist in any aspect of the disease, from diagnosis to initial treatment to treatment downstream. It’s always a fair question for patients to ask. Is there a clinical trial that may be appropriate for me? It is not limited to one segment of the disease.
Clinical trials are how we make progress. They are highly regulated and always have the needs of the patient front and center. At a minimum, a patient is always getting the option that is at least as good as the standard of care.
It’s a fair question to ask at any point along the way. Truly, all the options we currently have have only been possible because of patients’ willingness to participate in clinical trials.
As physicians, we are happy to have another set of eyes look at the patient and hear another person’s thoughts. That is in no way hurting your physician’s feelings by seeking out a second opinion.
Dr. Angela Fleischman
Dr. Fleischman: This may be a different answer than one may get in a community practice. When I approach a new patient and we talk about treatments, I’ll always talk about standard-of-care treatments first and give people their options, and the pros and cons of each of the standard treatments.
Afterward, we’ll discuss potential clinical trials that the patient might be eligible for. I talk about clinical trials at my own university or elsewhere that I think would be appropriate for the patient. If there was something specific that I thought the patient would be ideal for, we’d talk about that trial first.
Because I want to give the patient all of the information, I would talk about other clinical trials that the person may be eligible for. I would give them reasons why they might be a good idea but also why I don’t think that clinical trial would be ideal for them and give them specific reasons why.
I highly recommend second opinions or even third opinions. Sometimes patients feel bad going for a second opinion. Their primary oncologist may think that they are not happy with their approach. That is not the case.
As physicians, we are happy to have another set of eyes look at the patient and hear another person’s thoughts. That is in no way hurting your physician’s feelings by seeking out a second opinion.
I highly recommend a second opinion or a third opinion, even if it’s just, “I want to learn more about my disease. I’m happy with my treatment now, but I want to get somebody else’s point of view, learn about my future, and what might the options be if this happens or that happens.”
All drugs must move through the steps or phases to ultimately be approved by the FDA.
Melissa Melendez
Trial Knowledge #1: Phases of Clinical Trials
Ruth: Melissa, clinical trials try to see if we can improve the standard of care and give more and better options to more people.
There are different phases of a clinical trial. What are they and what do they mean?
Melissa: I like to think of clinical trials as steps to drug approval. All drugs must move through the steps or phases to ultimately be approved by the FDA. If drugs are studied in new combinations or in diseases outside of their approved indication, they still need to go through all the phases.
For phase 1 trials, the treatment is tested in a very small number of patients. It could range from 20 to 40 patients. We’re testing dosage and looking at the safety and side effects.
Phase 2 trials typically build on phase 1 results. They try to determine the effectiveness and safety of the drug in a specific population. We’re trying to answer the questions of whether a treatment works and how well it works.
For example, there may be a phase 1 trial that tests a drug in blood cancer patients or MPN patients. After the phase 1 results, they determined that myelofibrosis patients showed the best response to the drug. The phase 2 trial now might only include myelofibrosis patients and they’ll be testing it in a larger subset, like 100 to 300 patients.
Researchers continue to monitor patient safety throughout the phase 2 trial and phase 2 studies with positive results will then move into the phase 3 trial.
Phase 3 trials are often referred to as randomized trials, comparing a new treatment against the best standard treatment. These trials can be done with anywhere from 300 to 3,000 participants. Researchers are trying to see if a new treatment has better survival outcomes and fewer side effects.
When a trial is completed and shows that the drug is in fact better than the standard of care or the best standard treatment, that’s when the newly investigated drug becomes a standard of care and will become FDA-approved.
By the time a clinical trial enters phase 4, the FDA has already approved the treatment. These trials are done in thousands of patients and they usually go on for many years.
Placebos are not typically used with patients in cancer clinical trials. But if a placebo is used, the person will also receive the standard treatment for their specific cancer.
Melissa Melendez
Trial Knowledge #2: Use of Placebos in Clinical Trials
Ruth: This one needs myth-busting. A lot of patients and care partners say, “I wouldn’t want to risk getting a placebo.” Are placebos used in myelofibrosis clinical trials?
Melissa: Ruth, I’m really glad you asked that because federal regulations require patients to know if a placebo, which is an inactive substance that looks the same as the one used as treatment, will be incorporated into a trial. An example of a placebo could be a sugar pill.
Placebos are not typically used with patients in cancer clinical trials. But if a placebo is used, the person will also receive the standard treatment for their specific cancer. In our case for myelofibrosis patients, the placebo will be in combination with active drugs so patients are receiving at least the standard of care. No one with active cancer would be treated with only a placebo because that is unethical.
When researchers do use a placebo, they must tell the patient that they have a chance of getting a placebo and that they will receive an experimental treatment at some point in the clinical trial, if not right away. For example, you may be assigned to the placebo group, but if your cancer gets worse, researchers will switch you to a study drug or new treatment.
The more you ask and open up the lines of communication with your team about potential treatment options, the more you learn.
Melissa Melendez
Trial Knowledge #3: Finding Clinical Trials
Ruth: For people who want to explore clinical trials, what can they do to find one for themselves? The ClinicalTrials.gov site isn’t the most user-friendly and that’s why the LLS Clinical Trial Support Center is in existence and is so important. Tell us about that.
Melissa: I agree that ClinicalTrials.gov isn’t the most user-friendly and can be difficult to use. ClinicalTrials.gov is a searchable registry and database of clinical trials conducted in the United States and around the world. It can be overwhelming and this is where the patient’s healthcare team and the CTSC can come into play.
Patients can talk to their doctors and learn more about clinical trials done at their home institution or outside of it. The more you ask and open up the lines of communication with your team about potential treatment options, the more you learn. This can help you better understand what options are available to you and feel more comfortable moving forward with a treatment plan.
The LLS created the Clinical Trial Support Center to arm patients with information to take back to their healthcare team. The CTSC provides a free service to patients. It usually takes under five minutes to fill out a form online. Don’t get overwhelmed. If you’re worried that you haven’t filled out enough information, please submit it anyway.
We reach out to patients within 1 to 2 business days; typically, on the same business day that we receive the referral. When you connect with one of the nurses, you can expect a teammate who will join you on your cancer journey.
We take your individual needs into account. We learn about your treatment goals. We educate the patient about trials and conduct a clinical trial assessment. This includes addressing barriers, such as travel, and discussing financial assistance through LLS or even outside organizations.
We search for trials and go through each one individually, which is a little bit different than other online services. We take an individualized approach and only send trials to patients that they’re likely eligible for. We send the results to the patient and encourage them to take them back to their doctors to discuss the results.
We provide patients with a non-biased, patient-friendly list of appropriate clinical trials. Ultimately, we work in collaboration with the patient’s healthcare team to decide if a clinical trial is right for them. We offer to reach out to the trial sites if there’s anything on the trial list that they would like to learn more about.
We have many patients that we’ve worked with for several years and developed a personal connection with them. We really strive to provide continuity of care throughout their journey. I always tell my patients that I’m just a phone call away and they can always reach out to me at any point with questions or if their disease or treatment changes.
Over time, trials may change. Additional trials may open up or some may have closed so I want to make sure that I can provide them with an updated search any time.
Our services are available to myelofibrosis patients as well as other blood cancers ranging from pediatric patients to adult patients. We even encourage healthcare providers to reach out to us. We do clinical trial searches for physicians in large centers and smaller community centers where they don’t have as many resources or staff.
The clinical trial landscape is pretty complicated. CTSC nurse navigators are here to break down the barriers to clinical trials that patients face to help them make informed decisions. We’re here to help and welcome any patient referrals.
We learn about each patient and take a personal approach to find out their treatment goals, their physician’s goals, and what they’re looking for in a trial.
Melissa Melendez
Trial Knowledge #4: Staying in a Clinical Trial
Ruth: What are the top three things that you do at LLS to help people stay in a trial? Talk about the challenges and the solutions.
Melissa: We learn about each patient and take a personal approach to find out their treatment goals, their physician’s goals, and what they’re looking for in a trial.
Barriers are the first challenge. Nurse navigators are proactive during those conversations on breaking down barriers that patients might face. Are these barriers financial? Will they have to travel if we find one that they’re interested in? Our solution to these issues is to find out if a trial offers financial assistance in addition to what we may offer at LLS.
We email trial coordinators and principal investigators and inquire about the treatment schedule. How many visits may the patient expect? Can they get labs at their home institution?
This is also dependent on what phase the trial is in. This may not be possible for phase 1 trials, but more possible for phase 2 or phase 3 trials. Can any of the long-term follow-up visits be virtual?
Communication is also another challenge. Our solution in the CTSC is to help break down the intimidating medical language or trial jargon. We try to use the simplest explanations and if patients want more in-depth or complex information, we can definitely adjust and provide that as well.
We always check on a patient’s understanding. When we’ve explained something or provided information, we may ask the patient to repeat what they understood and listen as they walk through that process with us. The more they understand, the more comfortable they feel when they’re making the decision.
Trial awareness is a challenge and we can help raise awareness through programs like this. We talk about trial myths and help patients understand the clinical trial landscape better. We help patients be more well-informed about trials that may be available to them and about personalized trial services like ours and the Clinical Trial Support Center at LLS.
At the LLS, our main hub is our information resource center through our information resource specialists, nurses, and social workers. You can call the 1-800 number Monday through Friday, 9 a.m. to 9 p.m. Eastern Standard Time.
We also have a chat option where you can do a live chat online, and that’s Monday through Friday, 10 a.m. to 7 p.m. Eastern Standard Time.
If for some reason you reach out to us outside of our business hours, you can always leave a message 24/7 and we’ll give you a call back.
We’re in a very exciting time for myelofibrosis… We can personalize FDA-approved JAK inhibitors for each myelofibrosis patient.
Dr. Angela Fleischman
Final Takeaways
Ruth: If you could leave people with just one message, what would that be?
Dr. Mesa: I would leave them with a message of hope. We have made a tremendous amount of impact and a much greater understanding of the biology of the disease, the genetic mutations, and why people progress. We are building on a base of very good medicines that have made an impact with the JAK inhibitors but to a new era of multiple different approaches.
I would heavily encourage patients to consider clinical trials where appropriate. Clinical trials will build on the base of these medications to try to drive progress further and further. We need your help and together we will continue to improve the therapy of diseases like myelofibrosis.
Dr. Fleischman: We’re in a very exciting time for myelofibrosis. In the past few years, we’ve moved from a single FDA-approved JAK inhibitor to four JAK inhibitors. We can personalize FDA-approved JAK inhibitors for each myelofibrosis patient.
There are a lot of opportunities for combination treatments that are moving forward in clinical trials as well as going beyond JAK inhibitors, trying to identify other key pathways to target myelofibrosis.
Melissa: In the CTSC, we educate, support, and empower myelofibrosis patients as well as other blood cancer patients to be active participants and have control over their treatment decisions with their healthcare team.
The Leukemia & Lymphoma Society wants to make a difference in patients’ lives through research, advocacy, education, support, and financial assistance. We want to see a future without blood cancers. We have a lot of free information for patients, caregivers, and healthcare providers to check out.
We’re a phone call away and we are here to help make clinical trials less overwhelming for patients and to help healthcare providers.
Ruth: We have covered an awful lot of information and invaluable insight from our experts. I know I speak for people living with ET, PV, and MF, their loved ones, and care partners when I offer our very sincere gratitude to you all for everything you do for our community.
Stephanie: Thank you so much, Ruth. I always appreciate the way you bridge the conversation for us.
Thanks so much to Drs. Mesa and Fleischman for the work that you do in the clinic and in research to help patients and families who are trying to navigate a myelofibrosis diagnosis and treatment, and all the decisions that come in between.
Thank you to our LLS clinical trial nurse Melissa Melendez for being there day to day and helping people who are overwhelmed by the topic of clinical trials.
We really hope that you walk away with a greater understanding of clinical trials in myelofibrosis. We hope to see you at a future program.
Special thanks again to GSK for its support of our independent patient education content. The Patient Story retains full editorial control.
Updated October 9, 2023. Originally broadcast September 20, 2023.
Quality of life and precision are top of mind for chronic lymphocytic leukemia (CLL) patients. Understanding the complexities of available treatments can help you optimize your CLL care and prioritize the questions to ask your doctor.
During this live conversation, panelists Dr. M. Yair Levy, director of hematologic malignancies research at Texas Oncology, and Dr. Catherine Coombs, a hematologist oncologist at UCI Health who specializes in CLL, discussed the latest in CLL care. The discussion was hosted by CLL patients, advocates, and administrators of the CLL Support Facebook group Michele-Nadeem Baker and Jeff Folloder.
This discussion covers the current landscape of CLL treatment and care options, as well as new CLL treatments awaiting FDA approval, factors doctors consider when starting or switching a patient’s treatment, encouragement for CLL patients to advocate for themselves, and each doctor’s outlook on CLL treatment and patient quality of life.
There is hope. Hope to live a normal life, and hope to see your kids and your grandkids grow up. There’s always hope on the horizon, in my opinion.
Dr. Catherine Coombs
Thank you to AbbVie and BeiGene for their support of our patient education program! The Patient Story retains full editorial control over all content.
This interview has been edited for clarity and length. This is not medical advice. Please consult with your healthcare provider for treatment decisions.
Michele-Nadeem Baker: I’m Michele-Nadeem Baker. I’m a medical and health journalist, but in addition to that, I am also a patient. I started advocating for other patients on my first day of treatment when I realized that there was so much unknown out there and to demystify things for my fellow patients and help them through their journey.
Jeff Folloder: My name is Jeff Folloder. I am a passionate patient advocate. I am now in year 14 of my little journey with CLL and I am living a great life. That’s why I became a patient advocate because I want to make sure that everyone knows that it is possible to live a great life with CLL.
First up, I get to introduce Dr. Catherine Coombs. She is a hematologist oncologist with UCI Health and she specializes in chronic lymphocytic leukemia. She also helps lead clinical trials, trying to find better ways to treat CLL. Dr. Coombs, tell me what drew you to specializing in CLL. We don’t hear that a lot.
Dr. Catherine Coombs: It was a long road. I went into medical school knowing I wanted to be a cancer doctor. I didn’t have any doctors in my family, but I do have a lot of family members with cancer. It always inspired me to be on the patient end of the oncologic relationship. That’s always what I thought I would do.
Now, I didn’t decide on CLL until my residency years. I looked for a research project right away, because that’s the only way to get into a good fellowship program is by doing research. It always was something I wanted to do regardless. I found a wonderful mentor in my time at Duke University as a resident, Mark Llaneza, where I focused on the underlying genetic risk of CLL as my residency project. That drew me to the field right away.
Then I saw all these other benefits of being a CLL-focused clinician, which is that the patients do really well and they live a long time. I love having that long-term relationship with my patients. I love blood cancers in general, but I would say the acute leukemias, which I had focused on a bit earlier on in my time as a faculty when I was doing a bit of both were hard because there are a lot of patients that we lose and I really admire the docs that do it. But I think for my long-term well-being, I know that it’s just so much more gratifying and less emotionally traumatic to be able to have patients that thrive for so many years and be able to really enjoy those relationships as the added benefit.
The therapeutics have just continued to improve over the 13 years since I first graduated medical school and started doing research.
Michele: We need more doctors like you. Dr. Coombs, thank you so much. I’d also like to introduce Dr. Levy, who is a hematologist oncologist at Texas Oncology. He is the director of Hematologic Malignancies Research and specializes in CLL. He’s also helped lead clinical trials in CLL. Dr. Levy, what drew you to CLL?
Dr. Yair Levy: Before moving to Texas, I actually did mostly chronic lymphocytic leukemia, but I’m a little older than Dr. Coombs. So back when I was doing it, it was still a relatively better outcome for this cancer, but we still lost some folks to chronic lymphocytic leukemia. However, if I reflect on my current experience, I don’t believe that I have lost a patient to chronic lymphocytic leukemia in the past decade. This is not because I have a shortage of patients. I’ve probably accumulated about 150. I’m not saying that the patients don’t die, but they don’t die of CLL.
So to live a normal life is the goal. Even though we still think of CLL as a treatable but incurable malignancy, for the most part, people are doing relatively well. Not to mention, not only are our treatments better in terms of efficacy, but they’re so much better tolerated.
If I reflect on my current experience, I don’t believe that I have lost a patient to chronic lymphocytic leukemia in the past decade. This is not because I have a shortage of patients. I’ve probably accumulated about 150. I’m not saying that the patients don’t die, but they don’t die of CLL.
Dr. Yair Levy
Jeff: We have an interesting topic for today’s program, Shared Treatment Decision Making: How To Be An Empowered Patient. This is something that strikes me right in my heart. I am a firm believer that patients who take an active role in their own care tend to have better outcomes, and this is actually borne out of clinical research.
I took an active role in my own care. I chose not to go in the specific direction that my first doctor wanted to go in, and I wound up at a large research hospital participating in a clinical trial. I’ve been living a great life as a result.
Michele: For me, treatment decision-making also came down to becoming an empowered patient and becoming health literate in CLL. The more I could learn from credible sources, for me, was better. I realized all patients are different and doctors, you can probably relate to this more than anyone but the world has changed quickly and pretty drastically for clinicians, researchers, and those of us who are patients.
I was diagnosed 11 years ago, not quite as long ago as Jeff, but still a long time ago. My frontline treatment started in 2015 and things were even different back then. I was on a trial that combined ibrutinib, which at the time was not approved yet for frontline treatment. It had been for relapsed and refractory but not frontline treatment. It was combined with FCR, the standard at the time, fludarabine, cyclophosphamide, and rituximab. Things have changed so quickly even since then. In my frontline treatment, I’m now on a different treatment. I had relapsed in between.
Dr. Coombs, could you tell us how the landscape of treatments for patients has vastly changed over the last couple of years?
BTK Inhibitors
Dr. Catherine Coombs: Over the past decade, but even over the past few years, we’re seeing advances. When I first got into the field, yes, it was chemoimmunotherapy for patients fit enough to receive it like FCR and BR. With the introduction of targeted agents, largely chemoimmunotherapy is not widely used. However, we still do see about a third of uptake looking at these large-scale studies across the country.
I’d say that doctors who are focused on CLL realize that chemoimmunotherapy is not worth the toxicity. Its efficacy is also inferior to these novel drugs that are more efficacious, so more likely to put the CLL at bay, in remission, and delay time until ultimate progression, but also hugely safer. That was first ibrutinib, as you wisely know from your own personal experience and your knowledge over the time of your journey as a patient. But now we have a lot of newer and better drugs. Ibrutinib has been amazing and revolutionary, but it does have some side effects. Fortunately, they’re not so common, but they still can be clinically significant.
The first category of drugs that have really changed in the past few years is newer generation BTK inhibitors. Ibrutinib was the first in class. It inhibits this critical protein that’s part of CLL cell machinery, BTK, but it’s not totally selective for its target. We now have 2 additional drugs that inhibit BTK – acalabrutinib and the most recent addition, zanubrutinib which was FDA-approved in January.
The advantage of both of these drugs is that they’re more selective for their target, BTK. That, fortunately, has translated to improved safety, where both drugs have been compared head to head with ibrutinib and they demonstrate improved tolerability, specifically lower rates of atrial fibrillation for both drugs. Acalabrutinib also has the advantage of lower rates of hypertension.
What we don’t know is whether zanubrutinib is better than acalabrutinib or acalabrutinib is better than zanubrutinib, because we don’t have that comparison. But I think they’re both excellent options and both offer advantages over the ibrutinib days when we were dealing with a lot of atrial fibrillation. There’s a lot less in the way of that.
The other huge class of drugs that I haven’t mentioned is a completely different way of treating CLL, so I’ll mention it briefly. I don’t know if we’re going to get more into the nitty gritty on this, but these BTK inhibitors work wonderfully at controlling CLL, but they’re considered as treat-to-progression regimens, meaning that patients go on and stay on as long as they’re, number one, tolerating it and their CLL is responding favorably.
Some patients don’t like the idea of being on a drug indefinitely, so the other huge therapeutic advance over the past few years that’s been widely available is the drug venetoclax. This is typically combined with another drug called obinutuzumab when used in the frontline setting. Because it can so effectively kill off the CLL to very deep levels, patients are able to completely stop treatment after one year and then eventually relapse, but it can take a long time. That’s one of the other major, major changes in CLL just over these past 5 years or so.
I’d say that doctors who are focused on CLL realize that chemoimmunotherapy is not worth the toxicity. Its efficacy is also inferior to these novel drugs that are more efficacious, so more likely to put the CLL at bay, in remission, and delay time until ultimate progression, but also hugely safer.
Dr. Catherine Coombs
Michele: Dr. Levy, what else would you add?
Dr. Yair Levy: Dr. Coombs, you hit the nail on the head. It’s a dramatic change from chemoimmunotherapy. In the chemoimmunotherapy era, our high unmet need was what we considered high risk which were ones that harbor a 17p deletion, or a mutation in this TP53 tumor suppressor protein, or these cells of origin that are called pre-germinal cells of origin. So a more immature cell that had gone bad, and we’ve known that they have done historically quite poorly with chemoimmunotherapy.
As Dr. Coombs mentioned, the biggest improvement that we saw was when we actually recognized druggable targets within the B-cell receptor pathway. The first such drugs were actually not Bruton’s tyrosine kinase (BTK) inhibitors, and they are largely relegated to the history of the B-cell receptor pathway now. But these were the PI3K delta inhibitors. Those worked irrespective of cell of origin, and they also worked in the 17p deletion. So again, they did certainly have some tolerability issues and the efficacy was not comparable to those of Bruton’s tyrosine kinase inhibitors, which is one of the big reasons that those have really fallen out of favor.
As Dr. Coombs mentioned, the BCL2 inhibitor venetoclax has also been a game changer. We’ve been utilizing these agents, either alone or in combination with CD20 monoclonal antibodies. Now, the European Medical Association has even approved the combination of a BCL2 and a BTKi. This is something that we’re doing further studies on within the United States as well because we’re seeing that people achieve very impressively high rates of response. More importantly, very deep responses can allow, hopefully, a very long treatment-free interval, and perhaps even in some cases, a functional cure.
So, in the beginning, we were saying that CLL is largely treatable but incurable, but we put an asterisk on that. Even with chemoimmunotherapy, there was a subset of CLL that may have been cured by chemoimmunotherapy, or at least a functional cure. I think we’re going to see the same thing with these other combinations as well.
We’re seeing that people achieve very impressively high rates of response. More importantly, very deep responses that can allow, hopefully, a very long treatment-free interval, and perhaps even in some cases, a functional cure.
Dr. Yair Levy
How CLL doctors are providing CLL patients with precision care
Jeff: This is exciting stuff. We’re talking about an awful lot of options for patients, but before we can get to those options, we need to figure out how we get to that point. So let’s chat a little bit about the tests that are needed to diagnose and then accurately inform those potential treatments.
A lot of us in the support groups and on social media love tossing around the cute names, the FISH test, the flow test. Not a lot of people truly understand what’s going on with those tests. They don’t understand the concept of chromosomal abnormalities that may be going on with a patient at the time of diagnosis. Dr. Coombs, can you briefly give us a top line as to what these tests are doing and more importantly, what they’re telling you in terms of prognostics?
Dr. Catherine Coombs: Absolutely. Before the advent of all these, let’s call them sophisticated tests, we would stage patients. That’s always what I think cancer patients think of, what stage am I? We do have a staging system called the Rai Staging System that we use in the US. In Europe, they use this Binet Staging System. But the idea is, how much is this really affecting me? Rai stage 0 is when it’s just a high white count to Rai stage 4 when you have low platelets from the CLL.
I’m taking a step back because there were, for decades, ways of saying this a good or a bad CLL. However, what we’ve learned over the years is that there are some patients with really early-stage disease that would follow very aggressive clinical courses and then some that may have been technically a Rai stage 4 that were totally stable for decades. The goal with all these more sophisticated tests was to better predict, how is this person’s CLL going to behave, which then helps us as clinicians know what to expect. It helps the patient as far as what he or she should expect.
So taking a step back, we now have a lot of advanced testing that we can send. The good news is that these can be sent on the peripheral blood so it’s not necessary to get a bone marrow biopsy early on. Of course, we do consider these at the time of therapy, but we can send these tests in the blood because the CLL, by its nature, is circulating in the blood. So we can pick up different abnormalities that can tell us, this is a good or a bad CLL or maybe somewhere in the middle to help us, number one, know if we should follow this person more closely. Number two, is this someone that perhaps it’s less likely to cause more trouble than not?
The categories of tests are looking at the DNA, which is either via a FISH test which uses fluorescent probes to find common abnormalities that are known to be seen in CLL. The most adverse is the 17p deletion. On the other spectrum, the most favorable is an isolated 13a deletion.
However, what we’ve learned is that this is only looking at certain probes. Sometimes you can have other abnormalities that aren’t present as part of the FISH panel. In my own practice, I also send a karyotype test which looks for the same thing, abnormal chromosomes. Instead of using a preselected panel of common abnormalities in CLL, it just looks at all the chromosomes. The chromosomes, just for the patient’s knowledge, are just the big chunks of DNA that live inside every one of our cells. We’re focusing on what these abnormalities are in the cells because there are common patterns. There are good patterns and bad patterns.
It’s also bad to have a complex karyotype, meaning 3 or more abnormalities in any given cell, so that’s one category. The 17p deletion I mentioned is known to behave more aggressively. It’s still a chronic disease, but those are often the bad actors, especially back in the chemo days when chemo doesn’t work well at all. It does do better with our new drugs, but that is a particular problem because it deletes a copy of this very important gene called TP53.
We used to think the only way of losing that gene was by completely deleting the part of the chromosome where it’s contained. What has been learned over the past 10 to 15 years now in CLL, is that it may not be deleted, but it could be mutated. That’s another test that I think is very wise to send, especially in patients who are going to need treatment because a TP53 mutation is largely the same as a 17p deletion. There are a little bit of nuances there, but these are 2 separate tests. They both give similar information because those 2 abnormalities are treated as one and the same as far as their impact on prognosis.
The next category of testing is looking at the immunoglobulin heavy chain status, so a normal B-cell over its life. CLL is a cancer of B-cells that undergoes a process of somatic hypermutation where it just acquires mutations. It’s actually good to have a mutated, immunoglobulin-heavy chain. The bad finding is for that to be unmutated, which suggests this is a bit more primitive of a cell. And what’s been borne out through a lot of studies is that patients with unmutated are the ones who need therapy quicker and they don’t respond as well to certain therapies. Now, again, the negative predictive impact of some of these abnormalities is somewhat outdated. Sometimes they do just as well with our new treatments, but they definitely don’t do as well with the old treatments.
The other test I always send is the beta-2 microglobulin (B2M), mainly because that goes into our scoring system for CLL, the CLL International Prognostic Index, but it’s an adverse finding to have that elevated. I think that wraps up the bulk of all the prognostic tests that I send at the time of meeting a new patient and trying to help understand what is our future going to be like.
The goal with all these more sophisticated tests was to better predict, how is this person’s CLL going to behave, which then helps us as clinicians know what to expect. It helps the patient as far as what he or she should expect.
Dr. Catherine Coombs
Jeff: Let me play that back for just a second and put it in terms that are not quite so technical. You have a toolbox, and that toolbox has a lot of really nifty tools in it, where instead of saying you have leukemia or you have chronic lymphocytic leukemia or you have one of these genetic abnormalities, you’re able to hone down to a very precise level of differentiation. That’s where the term personal and precision care comes in. Correct?
Dr. Catherine Coombs: Excellent explanation. Yes.
Michele-Nadeem Baker: I love this term and how that is happening more and more for patients. Dr. Levy, before planning treatment, what do you like to understand from your patients so that you can learn more about them when it comes to prescribing their treatment?
We need to speak with the patient and find out what is most important to them and explain everything about the treatment, including side effects, logistics, expected outcomes if you choose one route versus another, and the cost of travel. There are a lot of things that go into everything.
Dr. Yair Levy
Dr. Yair Levy: We’re all different and everybody’s cancer is also different. The reason that we have jobs as oncologists is because, I’m not sure that’s true here, but hopefully we know more about CLL and the treatment options than the patients. It’s our job to explain to them all their various options and then help them arrive at a choice that makes the most sense for them.
I think Dr. Coombs mentioned that we have a lot of options, but they haven’t necessarily been compared head to head. So we can’t tell you prospectively how treatment A compares to treatment B or treatment C. There are certain guidelines of what’s called preferred therapies and other alternative therapies that are also acceptable. We need to speak with the patient and find out what is most important to them and explain everything about the treatment, including side effects, logistics, expected outcomes if you choose one route versus another, and the cost of travel. There are a lot of things that go into everything. This is our job to get them to ask the right questions and then answer those questions.
The role of patient comorbidities in CLL care
Michele: And what about comorbidities? Is it important for patients to discuss their other health issues with you, such as cardiac issues? There’s a myriad of so many other types.
Dr. Yair Levy: Absolutely. This is what we were saying is, we’re all different, we all have different things that matter, and we are all in a different place in our lives. We take all of that into consideration, there’s no question about it.
The comorbidities are incredibly important, but we certainly advanced past where we were 15 or 20 years ago when we were looking at whether patients are fit enough to take therapy versus not because right now we’re not necessarily looking at fitness for therapy as much as we’re looking at what is the optimal therapy for them.
Many of the therapies that we have, if you take a look at what’s called the Preferred Category 1 recommendations from the NCCN Panel, were all studied in what we would have technically called a non-fit population before. It’s wonderful that we have all these highly effective therapies that we can give to people, even if their fitness is not optimal.
The benefits of watch and wait
Jeff: We’ve been talking about a whole bunch of novel therapies, stuff that has really impressive outcomes these days. Michele and I will both be able to tell you without hesitation, that the first thing that most patients encounter is not treatment. It’s this thing that we call watch and worry. You guys call it watch and wait. CLL does not always need to be treated right away. Your medical team is going to work with you to decide when it’s best to start treatment. In the meantime, the patient’s worry. Did I sum that up correctly, Michele?
Michele: We sure do, even though we tell everyone not to and to take a breath when they’re first diagnosed. Jeff, you and I both know that we still go through that when we’re back in that time period. It’s just so counterintuitive to not be treated right away when the disease has not progressed where it ends up going when you do get treated.
Dr. Coombs, what are you looking for when it’s time to treat? You go through years, hopefully, during watch and wait. Worry and wait, as patients call it. But what is it that you’re looking for and is there any benefit to treating it sooner as with some of the other cancers out there?
Dr. Catherine Coombs: I’m coming straight from my clinic. I’m in a clinic room. I just had this conversation with a patient who is newly diagnosed about watchful waiting, which I totally understand why it’s watchful worrying for many. I always see it as my duty to help them understand why this is our approach. I acknowledge this is not what we do for many other cancers where you hear, find it early, treat it early. I wish our treatments were so good that treating it early would knock it out and you’d never have to worry about it again. In 2023, we haven’t been smart enough to come up with something that will do that for CLL.
The way that I help put that in context for my patients is this disease can be so indolent that maybe up to 1 in 3 patients never need treatment in their lifetime. So if we treated everyone, inherently we’re over-treating people. I hate giving people things they don’t need because every treatment comes with a cost, whether it’s financial or side effects. That’s my one very strong argument for not over-treating. But also, none of the early treatments that we have tried and done clinical trials on have been shown to make patients live any longer. That is just where we are.
I definitely could understand the frustration on the part of patients because that leaves you with these worries. I do see those getting better in patients as time goes on. There’s this initial period of uncertainty, but then as you see what your pattern is, that either tells us, maybe we are approaching the time for therapy or nothing’s really changing, I feel fine, and this is something I can accept.
Now, obviously, we never know which camp a patient is going to fall into in these prognostic tests. They help us have a general sense of, maybe this will be a super slow CLL versus one that progresses more rapidly, but nothing is certain. I do personally have enthusiasm for making this change.
There is an ongoing countrywide clinical trial looking at early intervention for patients with high risk. That is open at my own institution and across many, many institutions in the country. I really hope things will change so we can improve patients with early disease. I don’t think it’s going to be every patient because of this third that never needs treatment. I don’t ever see a reason to just treat everyone, but the trial specifically is focusing on high-risk patients. Maybe there will be some movement there. It’ll probably take about 10 years to find the results of the study because you have to follow patients for a really long time.
For now, my job is to not over-treat and not make people who are feeling good feel worse. If you’re asymptomatic, then the best I can do is leave you alone, but hopefully calm some of whatever natural anxieties come about with what is a life-changing diagnosis.
This disease can be so indolent that maybe up to 1 in 3 patients never need treatment in their lifetime. So if we treated everyone, inherently we’re over-treating people.
Dr. Catherine Coombs
Michele: We have some questions coming in from our audience. Dr. Levy, here’s one of the questions for those of us with liver enlargement. Should we watch and wait?
Dr. Yair Levy: I completely understand the anxiety that comes along with this. I’ve been treating indolent lymphomas for a couple of decades now, and I’ve got the same experience. You talk with patients, you tell them they have cancer, and then they’re saying, “You tell me I have cancer, but you’re not going to treat me now. Are you sure you went to medical school?” I had that come up several times.
By the way, we don’t do watchful waiting anymore. We call it active surveillance. Nobody likes watchful waiting, but if we’re saying we’re actively surveilling you, that sounds certainly a lot better.
The way that I explain it is, that there are really only two good reasons to treat you for anything. This isn’t just an oncologist, it’s in all of medicine. My wife is a real doctor, she’s an internist. She has the same parameters for treatment. So, number one, if you can make somebody feel better, that’s absolutely a great reason to treat them. Number two, if you can make them live longer.
What we’ve seen, as Dr. Coombs was saying in chronic lymphocytic leukemia, as well as a variety of other indolent non-Hodgkin’s lymphomas is that early treatment does not confer a benefit in survival. In other words, if we treat you when you’re asymptomatic, you’re not going to live any longer than if we wait to treat you when you are symptomatic. This is important because as we were talking before, our treatments are changing and changing for the better.
The treatments are becoming more effective and better tolerated. And remember, something is only incurable until we’re able to cure it. So there are a lot of good reasons to wait. Dr. Coombs mentioned this as well. If I can’t make you live longer by treating you earlier with our current therapeutics, the question is, can I make you feel better? If you’re asymptomatic, I can’t make you feel better. I can make you feel worse. I can spend a lot of your money, but I’m not helping you. You are the most important part of that equation.
If somebody has liver enlargement, the question is, are they symptomatic? Are they having pain? Are they having any other symptoms from their liver involvement? If they’re asymptomatic, I would not necessarily treat them just for liver enlargement. The same thing is true with spleen enlargement as well, which is a far more common finding in chronic lymphocytic leukemia.
If we treat you when you’re asymptomatic, you’re not going to live any longer than if we wait to treat you when you are symptomatic.
Dr. Yair Levy
Michele: I experienced that when I relapsed, but along with other things as well, which led to my going back into treatment. Dr. Levy, thank you. You brought up a lot of great reasons why people are not rushed into treatment which also hints at all the things that you do look at when it is time for treatment, which we’ll continue to talk about as we go through with our program today. Thank you very much.
Considering the duration of treatment for CLL patients
Jeff: We spoke earlier about a bunch of the newer options that are available. We know that the treatment landscape is changing by the minute. I’m going to tee this up in terms that forum participants and our support group participants, they all had the same questions.
Yeah, the drugs are great. Am I going to have to take them for the rest of my life, or is there a chance that I can do it for a fixed duration? Dr. Levy, let’s break down what those current treatments are, what baskets they fall into and is this a lifetime activity or could we end it in 6 months? Could we end it in one year? You’ve got a lot of stuff that ends in -ibs, and -tas, and -mabs, and all that. Explain to us what’s going on.
Dr. Yair Levy: Again, this treatment progression model is a relatively new phenomenon for us in the treatment of malignancies. We used to treat with a fixed duration of therapy when all we had was chemoimmunotherapy. You can understand why. Once we give chemo, we can’t take it back. Certainly, the effects of cytotoxic chemotherapy are not something that you want in a cumulative manner.
Because of the logistics of how cytotoxic chemotherapy works, we could not give that till progression because that would be a very difficult life. Everybody thinks that the worst thing in the world is dying, and no, the worst thing in the world is not dying. The worst thing is a long, crappy life. That’s what we would assure we would do to people if we continued them on chemoimmunotherapy.
If you take a look at our approved therapies right now, basically it’s two categories. Bruton’s tyrosine kinase inhibition, BCL2 inhibitors, and monoclonal antibodies, can be sprinkled on any of these regimens. In terms of approved fixed durations of therapy, it’s only with the BCL2 inhibitors. The reason for that is that’s the most ideal drug that we have seen in the treatment of chronic lymphocytic leukemia. What I mean by that is it is a killing machine. It kills so well that we had to attenuate the dose because if you kill things too quickly, that can also become a problem.
We’re able to get those very, very deep responses. These deep responses, even if they’re what’s called MRD, which stands for minimal residual disease, really should be measurable residual disease. Even if people achieve a level of disease below where we can measure it, we know that in many cases it still returns. We really need to get that logarithmic killing. We really need to reduce their tumor burden by many zeroes in order to give them that long treatment-free interval. Currently, that’s possibly more likely with a BCL2 inhibitor venetoclax.
As we were alluding to before, we are seeing combinations of Bruton’s tyrosine kinase inhibitors like ibrutinib, acalabrutinib, or zanubrutinib in combination with venetoclax. Again, this was based on these laboratory models in which they actually saw whether or not these cells were primed for death with this combination. They actually saw synergy, meaning that the drugs worked better together than the sum of their parts.
As we mentioned, this is a fixed duration of therapy that’s actually approved in Europe right now, but not here in the United States. In the United States, we certainly can give a fixed duration of therapy with venetoclax and a CD20 monoclonal antibody. I can tell you that anecdotally, I’ve also done that with Bruton’s tyrosine kinase inhibitor and a monoclonal antibody if I can achieve that very deep response.
In terms of approved fixed durations of therapy, it’s only with the BCL2 inhibitors. The reason for that is that’s the most cidal drug that we have seen in the treatment of chronic lymphocytic leukemia.
Dr. Yair Levy
Factors in choosing a first-line treatment for CLL
Jeff: Excellent. Lonnie’s got a great question. Since we’re now considering treatments, he wants to know what are the primary factors to consider in choosing a first-line treatment. Dr. Coombs How do doctors and patients make that call? How do you choose which drugs are up on deck first?
Dr. Catherine Coombs: I think there are disease-related factors and patient-specific factors. We tackle those one at a time. I think there is an important role in knowing what an individual’s CLL risk findings are because those can help inform how likely a treatment is to lead to prolonged remission. Specific to a venetoclax-based approach in the front line, what we do know is that there are shorter remissions in patients with the 17p deletion or TP53 mutation and also shorter remissions for individuals with unmutated IGHV.
I tend to be an optimist and so my view is that these therapies, venetoclax-based, work way better than chemotherapy ever did for patients with these high-risk features. We can still see lengthy remissions on the order of a little over 4 years for the 17p patients for progression-free survival or around 5 some years for the unmutated IGHV. That is shorter than if you don’t have those markers.
I do think it helps weigh expectations on what to expect from a time-limited regimen. If you have high-risk markers, if you have all favorable markers, venetoclax also works really well and it just works longer than if you had negative markers.
Now, Bruton’s tyrosine kinase inhibitors as a class that have really leveled the playing field. If we divvy up patients with the unmutated and the mutated IGHV and the chemo days, the unmutated would relapse years faster than the mutated. There’s not much of a difference, and so those drugs work really for everyone. Now, they’re just so different conceptually and side effect-wise, which is why it is so important to weigh the patient’s comorbidities.
In addition to these disease-related factors that could help gauge the relative success of any given therapeutic approach, there are patient-specific factors. That’s why it’s so important for me to know, not only the details of the CLL but also the details of your specific comorbidities. Do you have a high degree of cardiac comorbidities where maybe we might be a little bit nervous about the BTK inhibitors, which can have cardiac side effects?
I will say the newer drugs are much better than ibrutinib, but it is something I weigh whether you have significant kidney disease, which might be a little bit risky. When we think of a drug like venetoclax that causes tumor lysis syndrome – none of these are complete no-goes, but they help tip the scale of which one are we favoring a bit more.
Then, of course, I want to know what other medications you’re taking, because a lot of medications can interact. That’s something we have to make sure of. Often that’s not a big deal, we just switch one out, but we have to know.
Lastly is social factors. What are your preferences? Are you the type of person who wants to do everything and doesn’t mind a frequent schedule, but wants that payoff of then being done with treatment in a year, where we might lean more towards venetoclax-obinutuzumab? Or are you someone who wants to spend as little time at a doctor’s office as possible and is okay with indefinite treatment where we may lean more towards BTKi? Those are the 3 major categories I think of – disease factors, patient comorbidity, specific factors, and then social and preference.
My view is that these therapies, venetoclax-based, work way better than chemotherapy ever did for patients with these high-risk features.
Dr. Catherine Coombs
The benefits of monoclonal antibodies for some CLL patients
Michele: Dr. Coombs, thank you for talking about the biomarkers that might indicate someone is a high risk, such as 17p or TP53. I am high-risk, but I don’t have either of those. I have the other that you had discussed being unmutated IGHV, and that actually impacted my treatment decision when I relapsed. I just finished. I am on acalabrutinib and was on a blinatumomab until a couple of weeks ago. It was obinutuzumab for 6 months along with the acalabrutinib.
Now, I will be staying on acalabrutinib indefinitely because I am considered high-risk. I had originally stated before that I started on ibrutinib. BTK inhibitors work for me and I just had adverse events initially and that’s why I went off. I had a couple of years of a drug holiday and then my doctor decided that while BTK inhibitors were still working, let’s go for it. I would still have another option with venetoclax.
Dr. Levy, why does a monoclonal antibody help? What does it add to the one-two punch? I know you talked about the different things that they’re addressing and being a killing machine, but why is it only for some patients? For example, what I’m on, acalabrutinib and obinutuzumab trials have shown that it specifically works the best. One trial was presented at ASH this past year for people like me who were unmutated. So, why only for some patients is it a benefit?
Dr. Yair Levy: Well, that’s a great question. The CD20 monoclonals were our first immunotherapy in the treatment of many B-cell malignancies. When we combined them with some of the targeted therapies, we didn’t necessarily see what we were expecting. In all of the trials with chemoimmunotherapy, adding a CD20 monoclonal improved progression-free survival. But interestingly, when we took a look at some of the studies that had arms that contained both ibrutinib, our first, covalent Bruton’s tyrosine kinase inhibitor in combination with a CD20 monoclonal or without those progression-free survival curves were superimposable. I think we were really surprised by that.
By the way, I need a button that says “I agree with Dr. Coombs.” Dr. Coombs was actually mentioning the fact that there are differences among these covalent Bruton’s tyrosine kinase inhibitors, and our first one had a less focused kinase profile. In other words, it hit other kinases, not just Bruton’s tyrosine kinase that we were trying to inhibit. One of the other kinases that it inhibited was something called ITK or IL-2-inducible tyrosine kinase. This led to antagonism of the CD20 monoclonal, which is why we got no benefit from the addition of the CD20 monoclonal.
This is not true for the other covalent BTKi, zanubrutinib and acalabrutinib. However, you’re seeing the combination with acala because that is FDA-approved and zanubrutinib does not have an FDA label in combination with a CD20 monoclonal. Do I have any reason to think that it wouldn’t work as well? I do not. There’s certainly data that supports that as well, that there are differences in terms of PFS for folks receiving the combination of zanubrutinib with a CD20 as well as without.
Now you can say, so why doesn’t everybody get a CD20 monoclonal? The answer is that there are trade-offs. Everything in life is a risk-benefit ratio. We know that, for example, there is this virus here in Texas, I don’t know if you guys have it too, called COVID. We know that for COVID, the CD20 monoclonal certainly antagonized an immune response to vaccination, as do the BCL2s and Bruton’s tyrosine kinase inhibitors.
Certainly, you are at more risk for adverse events and complications when you add additional drugs, so everything is a trade-off. We’re getting additional efficacy but at a cost. Our job is not to tell patients what to do. Our job is to have a discussion and come up with a solution that works best for them after we have a discussion and they are fully informed.
Now you can say, so why doesn’t everybody get a CD20 monoclonal? The answer is that there are trade-offs. Everything in life is a risk-benefit ratio.
Dr. Yair Levy
What CLL doctors consider before ramping up treatment and dosing
Michele: Thank you. Dr. Coombs, let’s talk about ramping up treatment. When you start treatments such as with venetoclax or even obinutuzumab, you start with smaller amounts and then ramp up to full dosing. Why is that?
Dr. Catherine Coombs: It’s different based on the drug. Let’s tackle obinutuzumab first. Obinutuzumab is the monoclonal antibody that can be paired with either venetoclax or acalabrutinib. It can also be used by itself less often. It’s a hugely effective drug, and it doesn’t really have that many side effects except for one that’s almost universal, which is these infusion-related reactions. Of course, it has other side effects such as impaired vaccine efficacy infections. It can cause low blood counts, but the one that’s universal is infusion-related reactions.
Instead of just giving patients their full dose of 400 mg daily, we…slowly introduce it so we’re more slowly killing off the cells in a way that’s friendly to the kidney and friendly to the rest of the body to minimize any potential risks from all this dead cancer cell debris.
Dr. Catherine Coombs
What they’ve learned over the course of developing this drug in clinical trials is that, instead of blasting patients with the full dose on the first day, the reaction seemed to be more manageable if you split the dose. The traditional way of administering obinutuzumab, the full dose is 1000 mg.
Instead of doing that all at once, which would make for a very colorful reaction in the infusion suite that no one nurse nor patient wants to be involved with is giving 100 mg on day one and then the other 900 mg on day two. Then of course you follow along with the rest of the schedule. The reactions, fortunately, are almost always on the first 1 or 2 days and then not long-lasting except for rare exceptions. That’s the reason for ramping up obinutuzumab, to make the reactions more manageable.
Venetoclax is a different story. As Dr. Levy mentioned, this drug is remarkably effective at annihilating CLL cells. But it’s not a good idea to kill any cancer just too quickly, because when you kill a cancer cell, all this dead cancer cell debris gets released into our bloodstream and our kidneys can’t handle that, even the best kidney in the world.
Instead of killing cancer rapidly by administering the full dose, it’s been learned through very well thought out and designed clinical trials that patients tolerate it better with less chance for dangerous tumor lysis syndrome, which is the term for complications from cancer dying too quickly, is to ramp it up. Instead of just giving patients their full dose of 400 mg daily, we give them a little whiff of venetoclax in week one, 20 mg, a little whiff the next week, 50 mg, and slowly introduce it so we’re more slowly killing off the cells in a way that’s friendly to the kidney and friendly to the rest of the body to minimize any potential risks from all this dead cancer cell debris.
Considering the side effects of CLL treatments
Jeff: Dr. Levy, I love the fact that you used the term risk management because that’s pretty much how I approached my entire journey, with risk management. We know that for most people there are going to be some side effects. There’s going to be some challenges when they start treatment. Can you give us a minute on, are they all going to happen upfront? And how do you manage them?
Dr. Yair Levy: That’s a great question. As Dr. Coombs mentioned, for the CD20 monoclonals, most of the reactions occur early and typically improve as you receive more of the drug. This is also true for the oral medications that we have. Most of the side effects, if you look at what’s called adjusted incidence, meaning how likely is it to happen per amount of time, it’s more likely to happen in the beginning. However, as we talked about, some of these therapies are indefinite progression or intolerance.
If you take a look at the cumulative incidence of events that continue to go up, there are certainly some events that are much more difficult to come back from. One that we worry about in particular is what’s called ventricular tachyarrhythmias, so getting a funny heart rhythm can actually lead to sudden death. It’s tough to come back from sudden death, isn’t it? One person’s done it right. They wrote a book about Him. One Person came back from the dead. A very popular book, but nobody else has done it since so we want to make sure that we give patients the safest possible therapeutics that we can.
Reasons to switch a CLL patient’s inhibitor
Jeff: Sometimes patients are told that they need to switch out their BTK inhibitor. There are a lot of reasons why this could be done. Dr. Coombs, can you tell us what’s going on with this?
Dr. Catherine Coombs: That is a common question, and that’s something that’s evolved over the years from having one option, just ibrutinib, to now having multiple options. In my own practice, I actually have switched patients for a number of reasons. I would say the reason that I consider switching a patient off of a BTK inhibitor to a different BTK inhibitor is if they’re having some side effect that’s negatively impacting their quality of life. I have switched patients from ibrutinib to acalabrutinib with very good success. I’ve also switched patients from ibrutinib to zanubrutinib, and I’ve even switched patients from acalabrutinib to zanubrutinib.
There have been studies looking at switching for side effects. About 70% of the time, the patients have improved tolerability on one of the newer drugs. There have been studies looking at switching to both acalabrutinib from ibrutinib and then switching to zanubrutinib from both ibrutinib and acalabrutinib and it seems to be a pretty uniform result where more often than not, the newer drugs are better tolerated than our oldest drug, specifically ibrutinib. I think that’s a very valid reason to switch.
The education point is, I would not switch in the setting of progression. That just is not a strategy that works more than a month or two and it isn’t really worth it. If you’re progressing on a BTK inhibitor of these FDA-approved ones, again, not speaking to switching from any of the approved ones, ibrutinib, acalabrutinib, or zanubrutinib, that is not recommended.
Now, I’ve heard of some occasional doctors just switching everyone off of ibrutinib. I’d say I talk to a lot of the community. I think most of us don’t do that because the side effects that occur most of the time are early on. I don’t use ibrutinib for my new starts, but I definitely have patients in my clinic who have been on it for years and they’re doing well. The old expression is if it ain’t broke, don’t fix it. Some people think, well, let’s just switch everyone. I don’t think that’s wrong, but it’s just not something that I’ve done for the reason I mentioned.
Jeff: Thank you for that. Makes complete sense.
I would not switch in the setting of progression. That just is not a strategy that works more than a month or two and it isn’t really worth it.
Dr. Catherine Coombs
New CLL treatments awaiting FDA approval
Michele: Doctors, there are so many types of treatment and clinical trials. Dr. Coombs, which ones are you most excited about that are getting closer to FDA approval?
Dr. Catherine Coombs: There are two that I’m going to mention. I’m excited about a lot of things, but the ones that I think are the closest to being approved potentially, I have no window into when the FDA actually approves things. One is a drug called pirtobrutinib. This is a drug that inhibits the same target as ibrutinib, acalabrutinib, zanubrutinib, and BTK, but instead of inhibiting it irreversibly, it is a reversible inhibitor.
The reason that that’s important is that when patients develop resistance to ibrutinib, acalabrutinib, and zanubrutinib, the resistance is shared by all of these drugs. So you can’t switch from acalabrutinib to zanubrutinib or ibrutinib to zanubrutinib, etc., if your patient is resistant because they develop most commonly mutations where the drugs bind. Pirtobrutinib binds at a different mechanism. It’s in a different part of the BTK molecule protein and it has shown very excellent efficacy in a very large study. I do think that that may attain FDA approval for CLL in the coming days.
It’s already FDA-approved for mantle cell lymphoma as of January, so there are ways to get it off-label, but I would much rather see it get full FDA approval to help with insurance paying for the drug when it’s needed. It fills a huge unmet need for patients who have progressed on covalent BTKis, especially after patients who have progressed following venetoclax where we don’t really have good options.
The other big category that Dr. Levy has alluded to is the combination of a BTKi plus venetoclax. Europe approved the combination of ibrutinib with venetoclax, which did not get approved in the United States. I can’t really speak about the reasons because I’m not involved with those discussions. I do wonder if some of it may be the toxicity of that regimen, which can be somewhat hard to tolerate, especially for older adults.
But what we know is that we have better BTK inhibitors with respect to tolerability. So there are a couple of trials that are looking at the combination of acalabrutinib and venetoclax that I do think hopefully will be positive trials that lead to FDA approval. That’s the other major category that I’m looking forward to. Those would be frontline treatment. You would use that combination as your first treatment. Whereas pirtobrutinib, if it gets approved, would be a relapsed treatment, at least for now. Things obviously change as time goes on.
It fills a huge unmet need for patients who have progressed on covalent BTKis, especially after patients who have progressed following venetoclax where we don’t really have good options.
Dr. Catherine Coombs
Michele: So your top two are pirtobrutinib and the combination of–.
Dr. Catherine Coombs: A BTKi plus venetoclax.
Michele-Nadeem Baker: Dr. Levy?
Dr. Yair Levy: I agree once again. There are other small molecule inhibitors, again, targeting that B-cell receptor pathway, which has really revolutionized the way that we treat a lot of these B-cell NHLs. In addition, the bispecifics, are certainly working their way into our armamentarium for non-Hodgkin’s lymphomas as well as CAR Ts.
Interestingly, one of the first articles that came out about CAR T was in chronic lymphocytic leukemia, despite the fact that our current constructs, these current autologous derived products are certainly not showing the same level of efficacy in chronic lymphocytic leukemia as they are in diffuse large B-cell lymphoma, for example. Nevertheless, I think that we are going to see some tremendous improvements in terms of the CAR Ts in chronic lymphocytic leukemia as well as the Bispecifics.
CLL doctors’ top takeaways
Jeff: So, Dr. Levy, I’m going to put you on the spot. What is the number one takeaway that patients should be grabbing from this discussion that we’re having today? What’s the top of the list?
Dr. Yair Levy: We’re doing so much better. As I mentioned at the beginning of the conversation, I have not had a patient die of CLL in the past decade. When we take a look at the high unmet need and again, Dr. Coombs was alluding to that. Folks who have progressed on a Bruton’s tyrosine kinase inhibitor and a BCL2 inhibitor are certainly the unmet need. We have a tough time finding those folks.
We’ve had some studies that have been languishing for accrual because it required folks to become double refractory. Again, we have a tough time finding those patients, which is wonderful. I don’t want to find those patients. I’ve put 2 people on in the past 5 years, and one of them was actually not even really refractory. He just wasn’t taking his medication. With CAR T, once I give it to him, he can’t take it, so this was more of me being paternalistic.
We’re doing so much better. As I mentioned at the beginning of the conversation, I have not had a patient die of CCL in the past decade.
Dr. Yair Levy
Jeff: Dr. Coombs, what is the single most important thing that you want patients and their caregivers to take away from this discussion?
Dr. Catherine Coombs: Jeff, we are friends now. It’s going to be hard to narrow down one thing, but I think if I have to say one thing, it’s there is hope. Leukemia is a horrifically scary word to hear for the first time, or maybe even after years of knowing that this is what you have. But all the treatments work extremely well and they work for an extremely long time. There is hope. Hope to live a normal life, and hope to see your kids and your grandkids grow up. There’s always hope on the horizon, in my opinion.
Encouragement for CLL patients to advocate for themselves
Jeff: What can patients and their caregivers do or ask if their local hematologist-oncologist isn’t quite looking at this new wonderful stuff that’s on the plate right now? What if they’re just going with the old stuff?
Dr. Catherine Coombs: That’s such an important question. And, you know, I think it’s tricky. I think it depends on what your personality type is. My personality is that I want to make everyone happy. I never want to offend anyone. I certainly understand the hesitation to question your doctor. But I think in the end, you just have to realize this is your life. If your doctor is not sounding up to date or if you’re just not getting your questions answered, then you deserve more than that.
I just think it’s so important to advocate for yourself or advocate for your loved ones if things aren’t adding up. I think our community docs are amazing. The ones that I interact with, I have no idea how they keep up with everything they keep up with. To put things into context, there are around 20,000 cases of CLL diagnosed a year.
When you think about the common cancers that have a majority of patients, they’re seeing lung cancer, breast cancer – those are like 200,000 plus cases. CLL ends up just being a much smaller slice of what they’re seeing every day, and it’s just very hard to keep up. I would say most community docs I work with very much welcome the second opinion because I can teach them something and then we now have a relationship where they’ll ask me questions and we can work together.
So, number one, don’t be worried about offending your doctor. Number two, most doctors aren’t going to be offended. Number three, if they are, well, I don’t know what to say about that, but I don’t get offended. Back when I was at UNC, I had patients go to Duke and the Duke patients would come to me. Sometimes it’s just good to hear things twice. I think if your doctor is offended, that’s a red flag on their own ego. I think all that we should want as your doctors is for you to get the information you need. That is your job to advocate for yourself, and almost all doctors are going to be totally happy with it. We can learn something from each other as we share in your care journey going forward.
There is hope. Hope to live a normal life, and hope to see your kids and your grandkids grow up. There’s always hope on the horizon.
Dr. Catherine Coombs
Jeff: Thank you for that and I love the way you put it. Patients should not be concerned about asking questions. They shouldn’t be concerned about saying, why not? If they’re having trouble getting along with their doctor, like you said, that’s a red flag.
Navigating what symptoms you should share with your doctor
Michele: We have some more patient questions, so here’s one of them. Sara N. asks, “How do I know when I should contact my doctor between visits? Do they need to know about every infection or just about CLL symptoms?”
Dr. Catherine Coombs: Sara, that’s a great question. I think in the digital age, we certainly can let doctors know about every single detail, but I think it’s good to set up expectations. I try to do this on my first visit or maybe my second visit if we don’t have time to cover it.
But what things do I always want to know about, and then what goes into the other category? I always educate my patients on red-flag symptoms. Things that for my patients on watch and wait, watch and worry, active surveillance, things that make me think, we need to get you in right away. Unintentional weight loss, drenching night sweats, fevers. I go through the list of the things I always want to know about – a rapidly enlarging lymph node, etcetera.
Then there may be other symptoms, and the ones I want to know about are the ones that are worrying you. I don’t want you to go to bed freaking out about something that may be nothing. Just send me a message and I’ll tell you, that’s nothing or I need more information. Maybe let’s have you come in. I’d say, it’s never wrong if it’s something worrying you. But of course, we all have to acknowledge it could get to be a lot of messages if it’s every single thing. I think you just learn that over time as you establish with a doctor, but I think it’s good to go through what things should I let you know about right away, and what things can wait. Then obviously there’s some gray zone where it doesn’t hurt to just pass the info along and then you can get back a message and not worry about that.
Michele: In looking at a patient holistically, so to speak, regarding these little things that we may not think are important, such as all these various infections – I keep getting sinus infections. I’m trying to think of some other types of infections. Maybe you could list those for patients, some of the ones that they might be seeing that you want to know about.
Dr. Catherine Coombs: We do see an increase in infections in our patients with CLL. I do like to get a general sense of how often patients are getting infections. If they have a primary care doctor who’s very responsive, I’m okay with them treating these infections. I’m also okay taking the lead, whatever works best.
But when they become really frequent, especially if it ends up with the patient landing in the hospital, I absolutely do want to know about that. There are some strategies we have to lessen the incidence of these infections.
Patients with CLL, a proportion of them, don’t make enough immunoglobulins. If you’re landing in a situation where you’re having a lot of severe infections, meaning pneumonia that you’re in the hospital for, or terrible sinus infections, etc., that may be a reason to consider this intervention called immunoglobulin infusions.
I definitely like to know about things that I can fix. I’m okay knowing about things I can’t fix too. The ones where it’s like, this would change what we do, those are especially important. The patients may not know that before messaging me, and that’s okay. It’s okay to just message because you don’t know and then I’ll tell you there’s nothing to do or let’s bring you in and talk about X, Y, Z.
I always educate my patients on red-flag symptoms…Unintentional weight loss, drenching night sweats, fevers.
Dr. Catherine Coombs
Jeff: Fantastic. I’m going to make this a little bit personal as far as what I hope people are taking away from this discussion. When I was first diagnosed with CLL, my doctor told me straight up that I was going to die in about 6 years, and that doctor got fired. My next doctor told me, “Don’t worry, we’ve got this. You might die with this, but you’re not going to die from this.”
Listening to both of you fantastic doctors talk about the landscape of CLL and even use the 4 letter word “cure,” I am convinced that I am going to be able to continue doing everything that I want to do, and I want to do an awful lot of things at some point. If my daughters’ are cooperative, maybe I’ll become a grandfather, but I’m going to continue knocking out half-marathons. I’m going to continue knocking out full marathons. I’m going to drink good wine and good whiskey. I’m going to eat well. I’m going to laugh a lot. I’m going to smile a lot and I’m going to share my story so that patients and their caregivers know that that can be their life, too. Michele, how about you?
Michele: I agree some of my key takeaways are that there are so many things in research and we have the potential of being approved in the somewhat near future, which is yet another option for us. As you had explained, it does work in a different way than the traditional types of BTK inhibitors we now have. I think this is fabulous to have yet another option for patients.
Also, I love what you said about what you really need to look for in your own doctor and not be worried about offending your doctor. This is so vital for patients. I ask a million questions and I encourage patients to do so so that they can become more empowered for their own care and self-advocate for themselves.
It’s been so great hearing you and Dr. Levy both talk about patients asking questions and encouraging them so that patients are not afraid of this. This is again, one of the things I had started doing to try to get rid of the mystique around care and treatment with people’s doctors. I continue to do that.
In addition with Jeff – and we’ll be toasting soon, hopefully in person about this with something more than water, which we’ve been drinking during the program – and that is to live life to its fullest and to live a normal expected life span thanks to doctors like you, Dr. Coombs and Dr. Levy. I thank you so much for joining us, both of you and I thank all of our audience members watching us.
Dr. Catherine Coombs: And thank you both for all the work you do in patient advocacy. Like 10, 15 years ago when the Internet wasn’t available, I think there’s so much more fear. To be able to bring light in a way that patients can understand is so hugely important. So thanks for what you do as well and for having me.
Special thanks again to AbbVie and BeiGene for their support of our patient education program all about building shared treatment decision-making! The Patient Story retains full editorial control.
Sharing from real-life experience, the panelists were Stephanie Chuang, founder of The Patient Story and non-Hodgkin lymphoma survivor, Dr. Matthew Matasar, Hodgkin lymphoma specialist at Rutgers Cancer Institute, Dr. Samantha Siegel, both a doctor and Hodgkin lymphoma patient, and Chelsey Gomez, Hodgkin lymphoma patient advocate and artist behind Ohyouresotough.
The discussion covered an overview of Hodgkin lymphoma, standard, and emerging first-line treatments, options for relapsed/refractory patients including immunotherapy and stem cell transplants, managing side effects, the importance of doctor-patient relationships and shared decision-making, and key takeaways about community support and focusing on the quality of life during and after cancer treatment.
I’m a non-Hodgkin lymphoma survivor, founder of The Patient Story, and first and foremost, a patient advocate. The Patient Story was born out of my own experience with cancer. At the time, as a patient, I was looking for humanized answers for what my life with cancer would look like.
We’re proud to partner with The Leukemia & Lymphoma Society or the LLS, which is the world’s largest nonprofit health organization dedicated to funding blood cancer research. They also provide a lot of education and services and that includes their information specialists who are just one call away to help with your questions. They also have financial scholarships and we’ll talk about that at the very end as well.
Last but not least is Imerman Angels, a wonderful peer-to-peer support group program. I used Imerman while I was a cancer patient and they will connect cancer patients and caregivers with mentor angels. They will use things like age, gender, where you live, and experiences to try and make that match.
We also want to give a special thanks to Seagen for supporting our educational program and allowing us to really do the work that we want to do in true patient education, connection, and space and provide it for free; that’s really important to us.
We want to stress that The Patient Story, The Leukemia & Lymphoma Society, and Imerman Angels all retain full editorial control of the entire program. A reminder that this is not meant to be medical advice or a substitute for medical advice. It is educational and we’re hoping that you’re able to take away great information tonight back to your own doctors and healthcare team.
Introduction
Stephanie: First up, Dr. Matthew Matasar, someone we’ve been able to work with before. He’s the chief of the Division of Blood Disorders at Rutgers Cancer Institute. He’s been a medical oncologist specializing in lymphoma for more than 25 years and leads clinical trials to try and find new and better ways to treat diseases like Hodgkin lymphoma.
Dr. Matasar, what drew you to lymphoma? What inspires you to do the research that you do and dedicate yourself to patient care?
Dr. Matthew Matasar: First of all, thanks for having me. I’m really thrilled to have this opportunity. What we’re doing together really matters and makes a big difference so thanks for making this happen.
I started out as a philosophy major back when I was in college, wanted to go into medical ethics, and then got sucked into oncology.
I saw oncology in general and lymphoma, especially as a place where I could make a difference, where being a really good doctor or being a crummy doctor makes a difference. I wanted to be the kind of doctor who listens to his patients, works with them as individuals, and understands that when they’re coming to me, they’re having the worst day of their life. I want to try to make it a little bit better using my brain and my heart as best I can.
If I do my job well, it’ll be better than if I don’t. These things matter and what I do matters. I feel this pride in knowing that what I’m doing is making a difference for people in my clinic, individual by individual, and by trying to develop newer, more effective, and less toxic treatments.
Maybe I could leave a little bit broader mark on the world. Trying to make a difference. What we’re doing here is trying to make a difference.
Stephanie: Yes, and you’ve been doing that and we really appreciate that you go above and beyond to help patients and their families.
Next up, from one doctor to another, Dr. Samantha Siegel, both a doctor and a patient, which is a really interesting perspective. Sam, I’m really, really grateful to have you here and lucky to get to know you. Thank you for all that you do.
We will get into your Hodgkin lymphoma story shortly but, first, we’d love to hear more about you outside of the cancer diagnosis because as we know, we are so much more than that.
Dr. Sam Siegel: Thanks for having me. I’m so excited to be here and to connect with you and all of the patients, caregivers, and community members.
I am one-half of a sandwich. I’m married to another doctor named Sam, but we got married before med school. Sam squared, Samwich, he Sam she Sam — a lot of iterations of that that are fun and interesting.
I’m a proud mom of three kids. They’re my best teachers in this world. They’re so incredible. Parenting them through cancer and through medicine has been very interesting. It’s always exciting. Our house is never boring.
I love jogging, painting, and playing guitar. I’ve recently become an enthusiast of ecstatic dance. It’s like a nightclub but during the day. No booze and kids are allowed. It’s just freestyle dancing.
I used to dance growing up and I’ve gotten back into it lately as a way to connect with myself and my body. I found it really helpful in healing from chemo and chemo treatment. I love dancing, music, moving through music, cooking, and food.
I’m hoping to unify how other people enjoy aspects of being alive and how we can talk to our doctors about how to tailor our cancer treatment to what matters most to us. That’s really important to me because if I couldn’t jog, play my guitar, paint, or work with my hands anymore, that would be pretty devastating to me.
All of that matters when it comes to talking with my doctor. I’m excited to be here as a doctor, as a patient, as a person, as a human being, first and foremost so thank you.
Stephanie: Thank you, Sam. I couldn’t have put it better myself. It’s not just about extending life, it’s the quality of life and even after treatment.
We will talk about the long-term side effects because we all want to live and get back to living the way that we know how and maybe better.
Up next, another awesome rock star. You may know her as the genius behind Ohyouresotough, which is amazing artwork. Chelsea Gomez, thank you for being here tonight. As a patient advocate, you’ve grown such a community yourself. Can you also tell us more about you outside of the diagnosis?
Chelsey Gomez: Hi, everyone! I’m so happy to be here.
I’m from Florida. I just turned 33 and have a daughter.
I’m a professional artist. I own my own cancer awareness brand named Ohyouresotough. If you ever see anything of mine, you’ll see that I like to cope with hard things with humor. It’s really important to see the lighter side because a lot of the cancer world is not so fun.
I love all things art. I use clay, I paint, and I do digital art. When I’m not doing art, I’m running after my daughter to do whatever she wants to do, like play Barbies. I’m really excited to be here. Thank you for giving me the opportunity to share my story, too.
Stephanie: We appreciate it. Without voices like yours and Sam’s, we wouldn’t have the platform that we have today. Both of your stories are on The Patient Story so thank you for being here and for sharing your voice to help other people.
What is Hodgkin lymphoma?
Stephanie: Let’s get down to business. We’re going to try to avoid medical terminology as best as possible. Dr. Matasar, what is Hodgkin lymphoma?
Dr. Matasar: Working through things without terminology is theoretically what we’re supposed to be doing all day any day. When we’re talking to patients, families, and caregivers, we try to help people make sense of their illness.
What is lymphoma? Lymphomas are types of cancer. They’re cancers of cells called lymphocytes or immune cells. Lymphomas collectively are cancers that come from and are of the immune system.
That’s not to say somebody who has a lymphoma has a bad immune system — far from it. In fact, most people diagnosed with Hodgkin lymphoma have perfectly fine immune systems. They’re not constantly sick with infections.
For whatever reason, some cells mutate or change in a way that makes them live too long and start making copies of themselves. Then those copies live too long and they copy and the copies copy.
Compounding that, your body sees these cells that are copying that don’t belong there and views them as foreign or not right. In a similar way to an oyster that has a little grain of sand in it, it starts making a pearl around it. The body reacts to these cells and causes inflammation and scarring to try to wall off these weird cells causing even more swelling typically in lymph nodes, although that swelling can happen outside of lymph nodes in other parts of the body as well. It’s that swelling that usually leads to people being diagnosed with this type of specific cancer.
Sam’s Hodgkin lymphoma diagnosis
Stephanie: Sam and Chelsey, you had symptoms and red flags that helped you figure out something’s not right. Sam, what was your experience?
Sam: I wasn’t feeling right. In hindsight, it’s interesting to go back and piece things together, but I felt this vague sense of tiredness. I didn’t have enough gas in my tank. I was still running 10 miles on the weekends, but coughing a lot.
I didn’t have the steam for my usual level of physical exercise. I was coughing a lot, particularly at night. There were a lot of California wildfires at that time so I thought it was the air.
And, of course, I’m tired. Every parent during the pandemic is tired, especially with our kids doing homeschooling. It’s a whole different world. Then being a doctor at that time was very hard.
But then I got a rock-hard lump that appeared above my collarbone. It was painless and rapidly growing. As a doctor, I knew that I had cancer.
I got a scan and mine said something about possibly metastatic lung cancer or breast cancer. They weren’t sure so I needed to get a tissue biopsy. A little bit of time transpired between noticing the symptoms and getting the tissue biopsied.
Once that came back as Hodgkin’s lymphoma, I knew what the path ahead would be like. Around the time I was diagnosed in 2021, there was this big change that started happening with immunotherapy. It was the standard of what had been happening for a really long time, which is ABVD or a combination of four drugs.
I got on the eve of my 30th birthday. Then I started ABVD.
There was a question about my staging, whether I was stage 2AE or stage 4 because there was some lung infiltration. Long story short, that meant that I was going to get six months of ABVD.
After a month or two, the coughing went away and I started feeling better. My cough came back at about month 2 to 3. We thought it was the bleomycin. I’m a runner and that’s very, very bad. We ended up dropping the bleomycin and I continued on AVD alone for the remaining four months.
Coincidentally, there had been a trial around that time to say that that’s okay, the de-intensification of therapy. Dropping the bleomycin became a standard thing, if people got a scan after a couple of months that showed that the body was responding.
My PET scan after two months looked really good. My cancer was responding and I was having that cough. We dropped the bleo and then I did four more months of AVD and boy, was it hard. It was really, really hard.
I had a lot of side effects. I struggled a lot and I struggled with that feeling. I hear people say about Hodgkin’s that this is the good one. It certainly didn’t feel that way. It felt really hard.
Stephanie: I hate when I hear whenever people say you got the good one.
Chelsey’s Hodgkin’s lymphoma diagnosis
Stephanie: Chelsey, how about you? What were the first symptoms for you or the red flags?
Chelsey: I was first diagnosed with Hodgkin’s in 2018 when I was 28. I was working a lot of hours so I was very tired, but I didn’t think much of it.
I had weight loss. I was trying, but it never worked before and then I suddenly started losing weight. I had shortness of breath and, at one point, I almost crashed my car because I had a vertigo episode. I ended up going to the doctor and they told me it was just stress.
The only reason I got diagnosed with Hodgkin’s was I eventually had a lump come up on the left side of the base of my neck. I went to urgent care. They told me that I just needed antibiotics, but there was something in their eyes that told me that wasn’t all I needed.
Eventually, my family forced me to go to the ER and we got a full biopsy done. I was in the hospital for the first time. Long story short, I had stage 2 Hodgkin’s and I also had ABVD. About halfway through, we had to drop below because I had toxicity.
I was re-diagnosed with Hodgkin’s in 2019 as well.
Dr. Matasar: First, hearing Chelsey, how you knew better, listened to your body, didn’t take no for an answer, and saw something that made more sense to you. The importance of that just can’t be overstated.
I meet so many patients who say, “Well, they told me not to worry,” or “My doctor told me to come back in six months and I was getting worse and worse, but I was told not to worry. I was told it was something else.” Congratulations on knowing better and I hope that people take heed and learn from the example that you set.
Chelsey: Especially when you’re young. It’s hard sometimes to speak up. But even if you’re young, you know your body.
Dr. Matasar: Maybe even especially if you’re young. We all know that old doctors sometimes don’t have the best reputation for listening to young people, trusting them, or taking them as seriously as they ought to be taken. Doubly so because of your youth at the time.
Changes in the treatment of Hodgkin lymphoma
Stephanie: Dr. Matasar, the treatment landscape in Hodgkin lymphoma has been changing quickly. Can you share about the evolution that’s been going on?
Dr. Matasar: Back in the ’80s, ’90s, and 2000s, clinical trials to try to make Hodgkin lymphoma better were all about intensification. How can I ratchet the treatment up to make it even stronger, even more toxic, but even stronger against lymphoma?
We were climbing that mountain of pushing to see just how much chemo we could cram into someone’s gullet in pursuit of a cure. All we had was chemo so what you want to do is more.
We’ve come over the other side of the mountain now and we’re in a very different place. As a discipline and lymphoma experts in the field, we’ve moved away from intensification.
We’re into de-intensification, personalization, and leveraging treatments other than chemotherapy as we try to help both maximize the chances of cure and minimize the short- and long-term risks of our treatment.
We’ve gone away from uniformly using ABVD, which remains a very good treatment and a very commonly used treatment.
More often, we’re now using other adjunctive treatments like brentuximab vedotin or ADCETRIS in lieu of bleomycin, which both Chelsey and Sam talked about potentially injuring their lungs, leading to cough or shortness of breath.
We’re finding ways to cure more people and, at the same time, cause less harm along the way and that’s really where the future of Hodgkin’s lymphoma is going to take us. We try to make even more progress on this mission towards more effective and less toxic treatments.
Stephanie: I love that that’s the trend and that we can continue going down that path.
First-line treatment for Hodgkin lymphoma
Stephanie: We’ll talk about some of these newer promising treatments and new directions, but can you tell us a little bit more about the standard first-line treatment for Hodgkin lymphoma?
Dr. Matasar: As oncologists, when we meet a Hodgkin’s patient for the first time and we work through their treatment choices, we think through those choices together with our patients and their families.
We split people into different categories as we understand the risk of their disease and the options that are presented because of that.
One first way to try to put people into categories to help them think through their choices together is based on stage. We talk about early-stage Hodgkin lymphoma and advanced-stage Hodgkin lymphoma.
People will often ask, “What’s my numerical stage? Is it stage 1, stage 2, stage 3, stage 4?” We heard from Sam that sometimes, it’s not even clear to us as oncologists exactly what the stage is. Is it a stage 2E or is it a stage 4?
The staging exercise, which sometimes feels very black and white, can have shades of gray. We do our best to try to put people into risk categories informed by their stage and then think through the treatments that we know are best for that stage of illness.
Early-stage Hodgkin lymphoma treatment
Dr. Matasar: For the vast majority of people with early-stage Hodgkin lymphoma, the standard of care remains to be ABVD. It’s been around longer than I’ve been a doctor. It’s an oldie but a goodie and it still will cure the vast majority of patients.
Sometimes we think about radiation therapy as part of that treatment and sometimes not. However, ABVD for early-stage Hodgkin lymphoma remains the standard of care.
Advanced-stage Hodgkin lymphoma treatment
Dr. Matasar: For most patients with advanced-stage Hodgkin lymphoma, we’ve moved away from ABVD. This is based on really powerful clinical research comparing ABVD to a program where the bleomycin was swapped out in lieu of this newer immunotherapy called brentuximab vedotin, which is a type of drug called an antibody-drug conjugate.
An antibody is a protein that binds onto the surface of a cell and stapled to that is a toxin so this conglomerate attaches onto the Hodgkin cell, the Hodgkin cell absorbs it, and then the toxin is released inside the cell — like a Trojan horse sneaking into the city and releasing the soldiers inside.
This newer program where bleomycin was swapped out for brentuximab — so BV-AVD instead of ABVD — not only got more people into remission and kept them in remission longer, but actually led to a higher cure rate, people living longer, and everything good that we as doctors want for our patients.
Because of this important research, we really now use brentuximab plus AVD as our traditional standard of care treatment for patients with advanced-stage Hodgkin lymphoma in pursuit of a cure.
Role of radiation in Hodgkin lymphoma treatment
Stephanie: You mentioned radiation therapy as well and that has been its own sort of beast, if you will. There are a lot of considerations about long-term side effects and where the mass is located. What role do you think radiation therapy has been playing? What are your thoughts about whether it should still be used and in what situation?
Dr. Matasar: It’s a great question and you’re right, it is sort of its own beast. Back in the ’80s and early ’90s, almost everybody with early-stage Hodgkin lymphoma got radiation treatment as part of their care.
We knew then and now that using radiation therapy would cure a few more patients than not, but that slight improvement in cure rate never translated to people living longer.
It’s a trade-off. You may do a little bit better with Hodgkin lymphoma in some situations but you’re paying a steep price oftentimes in terms of long-term effects, late effects, and risks of health problems later in life.
That includes radiation therapy putting patients at a higher risk for other cancers later in their life, particularly younger women who need radiation therapy to the chest. If that radiation touches the chest wall and breast tissue, particularly for women under the age of 35 or especially under 30, it really does heighten the risk of breast cancer later in life.
Your heart also doesn’t like radiation therapy much more than the rest of you. We know that radiation therapy to the heart can lead to a higher risk of heart disease later in life.
There are all these consequences of the decisions that we make together in our pursuit of a cure. Because we know so well about these late effects of radiation therapy, increasingly, we try to be ultra choosy with whom we use radiation therapy.
We really restrict its use for what we think we really need to get a cure. For most patients, we can cure them just fine without using radiation therapy and putting people at risk for health problems later in life because of that treatment.
Use radiation therapy if you need to; it’s a great treatment. It can be life-saving when you need it but don’t use it willy-nilly.
Side effects of Hodgkin lymphoma treatment
Chelsey’s side effects of bleomycin
Stephanie: Chelsey, you experienced the toxicity and side effects of bleomycin. Can you talk to us about what that reaction was and what you did about it?
Chelsey: I had my fifth chemo right before New Year. I had chemo four other times, but I went home and spiked a really high fever all of a sudden. As a cancer patient, if it’s 100.4°F, you have to go. Mine was 102 and my husband said, “We’re getting in the car.” I was very lethargic and just not feeling well.
We ended up in the ER and they told me I was septic. Of course, my mom heard that as well. She was watching my daughter and she’s freaking out because it’s not good when you’re septic. They put me in the ICU and I was in the ICU for at least two days.
The symptoms dissipated after a few hours. I was feeling better, not 100%, but they started giving me antibiotics around the clock.
I had a feeling that it had something to do with bleomycin. I’ve researched what can happen with bleomycin because I have asthma and that was something I had to consider going into the treatments.
Everything I was seeing was adding up to it being toxicity, but there was nobody at that hospital who really treated cancer patients. They came in and out, but they weren’t there all the time.
It took about four days for my oncologist to actually come and see me. At that time, I pretty much diagnosed myself with bleomycin toxicity. I also stopped accepting the antibiotics because it wasn’t an infection. It was a reaction to this drug and it was confirmed later on.
I also had a pulmonary function test and I had a 30-point drop or something. I’m happy to report that I have regained a lot of my pulmonary function now many years out. For a lot of people, I know that’s something scary when you do go through this.
This was a local hospital and they had never seen this before. The doctor was saying, “You need to advocate for yourself, especially when you’re in a situation where you know your cancer probably better than the people that are there. It’s not your regular care team.” I had to speak up for myself and it was hard, but I did it.
Stephanie: I really appreciate that you spelled that out. Dr. Matasar talked about it earlier, too, and I know Sam’s a huge proponent of that as well.
You said it was hard and I think we’ve all experienced that as patients where you want to advocate for yourself. You hear it from other people. It can be a little bit difficult to speak up. Do you have any other tips for people who are on the fence about it, who aren’t sure if they’re supposed to speak up?
Chelsey: I wasn’t a great advocate for myself when I first got sick. The oncologist I ended up with was the one who was just walking by when I was in the ER initially and I thought it was fate. It wasn’t. Immediately upon meeting him in his office, he told me it was the good cancer.
I was like a unicorn of the Hodgkin’s. Nothing went how it was supposed to go. It wasn’t good at all. Sometimes I was quiet about it. I didn’t know what to do because I always look things up and he would call me Dr. Google but not in a nice way. I was scared to bring up a lot of things.
If you’re young and you’re scared or sometimes it’s when you’re female and you have a male doctor, it can be intimidating. Bring your family with you or somebody else you trust and have them speak up for you if you are scared to do it. I know a lot of people do that and it’s helpful.
When you’re inside that room, your mind goes fuzzy and you don’t even know what’s going on half the time. It can be the difference between having a good result or ending up pretty much needing a transplant like I did. I truly believe that if I had been a better advocate, I might have not needed one.
Stephanie: Thank you for going into all that. I can completely attest to blanking out in the doctor’s office and not hearing the same thing that my family heard. I appreciate that tip about bringing people in if you can.
Sam’s side effects
Stephanie: In terms of side effects, you worked with your doctor to manage them. Can you share anything that was helpful there?
Sam: I had a lot of side effects. I had a lot of nausea and vomiting, yet I gained a ton of weight during AVD from all the steroids and I was developing a lot of problems from that. My glucose and liver enzymes were increasing. I had inflammation in various organs.
In hindsight, I think that was also making my neuropathy really bad because once my glucose got better and I lost weight, my pain and my nerves got better, too, despite the fact that I was getting more medicine that theoretically should have been impacting the nerves.
All your systems can be impacted. Taking care of the whole body is really important. I talked to my doctor about diet, lifestyle, and supportive therapy. What are some complementary therapies that I could try while getting my traditional medicines?
I also took a lot of medicine at the time. I needed pain medicine. I needed nausea medicine. I needed all the tools in the toolbox to cope with living day-to-day because it was just really hard.
The medicines caused a lot of mood and neuropsychiatric side effects. I had problems thinking. At some points, I had problems driving or following a list of simple items and that was really tough for me. That was a really far fall in terms of functioning, going from being a doctor to having trouble shopping a grocery list of five items so that was pretty devastating.
When I found out that I could do brentuximab as therapy leading up to the transplant, that gave me a huge quality of life back. As those other drugs cleared out and my body healed, I could think again and started feeling myself in here again. I’m not gone, I’m still there, and that mattered so much to me. It was a huge gift.
Stephanie: I really appreciate you bringing that to life because sometimes, we feel lost in that fog and how important it is to get any semblance of that quality of life back of ourselves. Your story shares that so powerfully.
Immunotherapy for Hodgkin lymphoma
Stephanie: We’re going to shift to combination therapy for the front line. Patient Matthew S. asks, “How successful have immunotherapy trials been in regard to Hodgkin lymphoma?” Dr. Matasar, can you explain the idea behind combination drug approaches and for whom would this benefit?
Dr. Matasar: We’ve talked about the progress that we’ve made with swapping brentuximab vedotin for bleomycin.
Matthew’s question about immunotherapy is a really valuable one. This idea of immunotherapy has really been a revolution in a lot of different forms of cancer, but nowhere has it been more impactful than in Hodgkin lymphoma.
When we talk about immunotherapy in Hodgkin lymphoma, what we’re generally speaking about is a class of medicines called checkpoint inhibitors.
One of the ways that these Hodgkin’s cells survive in our body is they are able to effectively shield themselves from our normal healthy immune system cells. They put up these barricades and ways of shielding themselves or hiding or preventing our immune system from doing the trash.
There are two checkpoint inhibitors that are approved for Hodgkin lymphoma, which are very similar medicines truthfully: one called nivolumab and one called pembrolizumab — we’ll call them nivo and pembro for short. These medicines are able to strip those shields off of the Hodgkin lymphoma cells and allow your immune system to see what it was otherwise blind to.
The treatment itself does nothing to the cancer cells. It does not kill a single cell all by itself. What it does is re-enable your own body’s immune system to do the work. It’s a game-changer.
When we use these medicines by themselves and use them as a treatment for a patient who’s been failed by many different prior chemotherapies, they’re able to put people into remission more than half the time.
They’re actually able to cure some patients. Despite chemotherapy having failed again and again and again, this medicine is able to eradicate the lymphoma. It goes away and never comes back. That’s amazingly powerful to be able to say and it’s an amazingly powerful treatment modality for patients with Hodgkin lymphoma.
The more we learn about how good these medicines work, the more we want to use them for more patients to try to help cure more people. It went from being a last-ditch effort after everything else has failed to be part of the treatment when it comes back. Using it in that situation was able to help more patients.
We’re now seeing the initial results of our first trials of using it as part of the first treatment. Instead of ABVD or brentuximab plus AVD, we’re combining nivo or pembro with chemotherapy like AVD and we’re starting to see very promising early results.
BV-AVD vs. ABVD as first-line treatment
Stephanie: How much is brentuximab and AVD being used? Is it standard of care or does it just vary depending on the hospital system or the healthcare provider versus going to ABVD first-line?
Dr. Matasar: It’s a little bit hard. Everybody’s situation is a little bit different. There are standards of care, which means that all things being equal, it’s sort of a one-size-fits-all approach.
Medicine is never that clean or that easy. There are times when ABVD would be a standard for early-stage disease, but we have to use brentuximab instead of bleo. There are people with advanced-stage disease who even if BV-AVD would be the standard, I still want to use ABVD for this individual patient.
This happens because doctors listen to our patients and we take into account their personal priorities, preferences, and individual risk profile. All of these medicines have their own pros and cons and their own risks and rewards.
A treatment program is best when it’s personalized and done in the context of a doctor and a patient having meaningful and valuable conversations about what matters to that person. Is it just a cure regardless of side effects? Is it being able to play the guitar and run? What is it about the treatment that we need to take into account as we map a path toward cure?
Stephanie: Any idea of when we could see the FDA approval of checkpoint inhibitors in the front line?
Dr. Matasar: Certainly not anytime soon. The first results that we had were read out at major conferences. This is still very early data.
When it comes to Hodgkin lymphoma, doctors were very conservative. We don’t want to mess this up. We know that the stakes are high and that many people will be cured with traditional treatments. We don’t want to change gears until we’re really confident that we’re not hurting people in the process.
The initial safety readout of this combination using the checkpoint inhibitors in the first treatment looked better than any of us expected. There are a lot fewer immune-related side effects than we’re accustomed to seeing when using these immunotherapies. They do have their own immune-related side effects.
We want to see the data mature, as we say. We want to see how people do over time and make sure that there are no dangerous signals about increased late effects or late side effects happening as we gain more experience with this treatment approach.
Long story short, we don’t want to change anytime immediately soon. We’re probably looking a couple of years down the road.
Treatment for relapsed/refractory Hodgkin lymphoma
Stephanie: Dr. Matasar, how have the standard of care treatments for relapsed/refractory Hodgkin lymphoma patients been changing?
Dr. Matasar: Historically, when chemo failed, we would use other chemotherapy programs that use different chemotherapy medicines than the first cocktail. The most commonly used in America historically was a program called ICE: ifosfamide, carboplatin, etoposide. Different than ABVD because they’re different medicines, but still chemo.
We’ve moved away from ICE being the only standard of care and we’re using more of those other medicines — brentuximab, the checkpoint inhibitors. You can use one of them all by itself or in combination.
It’s informed, of course, by what we did the first time. If patients get brentuximab as part of their first treatment, we’re not going to rush into doing it a second time and want to do something a little different. Maybe we would use checkpoint inhibitors alone or combined with some milder chemotherapy programs.
This is the art of medicine. Trying to pick amongst a number of very effective choices and determining how to leverage those medicines and combine them to achieve our patient’s goals. Always with this view of maximizing the good and minimizing the bad.
Sam’s Hodgkin lymphoma relapse
Stephanie: Sam, you relapsed a month after finishing your first-line treatment. I can’t even imagine what a gut punch it was to go through all that and then find out that news. What was that conversation like about where you were going to go next?
Dr. Siegel: Gut punch is a really great way to put it because it was. I finished six months of ABVD, which then went down to AVD. Despite a scan saying that I had no evidence of disease, I felt pretty awful.
At that point, I wasn’t sure. Am I just feeling awful because this is just what a body feels like after you’ve had six months of this poison? Something in my gut was telling me that something wasn’t right yet, but my scan was clean so I just focused on recovery for a little bit.
Within a month, I started having symptoms that were eerily reminiscent of my initial symptoms — a wheeze only in the left upper part of my chest and a little pea-sized lump. That time around, I thought, Okay, I think I’m pretty clear what’s happening here.
I got a scan, which led to some biopsies and a diagnosis of a relapse. I’m already researching on Google the next treatment regimen that I’m going to have to go through. The whole while, I’m preparing myself that I’m going to have to go through ICE.
I’m thinking for sure I’m going to have to go through something called ICE, DHAP, or one of these other regimens that have been used longer term for relapsed/refractory Hodgkin’s or salvage therapy.
When the relapse was confirmed, my doctor said, “There’s this drug now, a targeted therapy called brentuximab. Instead of doing ICE, would you be open to trying that alone for a couple of months and then repeating a PET scan to see where we’re at?”
There was a pretty decent chance that if the brentuximab didn’t get me into remission before the transplant, I would have to get ICE, a multi-drug, more traditional chemo. I was willing to take that chance because I felt so beaten up by having to get all those months of traditional cytotoxic chemotherapy and all the side effects.
The decision made sense to me at that time whereas maybe other people may have been, “No, I want to hit it hard and do that right away.” For me, I was going to take the least amount of poison possible to get me into remission before transplant.
It worked. I got a strong remission before my transplant. I went on to get the bone marrow transplant then I took brentuximab. I did almost a year of post-transplant consolidation treatment.
Because those studies and the data were just coming through, my doctor said, “You know, this is kind of becoming a thing now based on the research and this seems like it might really fit you based on how bad you’re feeling,” so that was perfect for me. I was so grateful.
Stephanie: The timing matters, right? It just happened.
Stem cell transplant
Dr. Matasar: The first thing to say is that there are two types of transplants. What we’re talking about so far is a treatment called autologous, or from yourself, stem cell transplant.
To call it a transplant is actually wrong. There’s no transplantation going on; it’s just a word that we use. This treatment that you’re hearing from Chelsey and Sam is basically just a trick. It’s a way of letting us give a round of super strong treatment.
With regular strength treatment like ABVD or ICE, we give those treatments and then let people recover. Sometimes if the chemo is stronger, you might need to boost the recovery.
Here, we’re talking about a single course of treatment, usually six days, that is so strong that if I gave it to my patient, gave them a hug, and said, “I’ll see you later,” I wouldn’t see you later. It’s too strong.
We need a very powerful antidote for such a powerful treatment. The antidote that we use is actually a person’s own stem cells, these special Adam and Eve progenitor cells that live in our bodies and let us heal.
We filter the blood ahead of time with a process like a mini dialysis where we filter out a few of those special stem cells. We put them in the freezer, give people six days of chemotherapy, thaw out those cells, and give them back as an antidote.
The course of the six days of treatment and the stem cell re-infusion as a little mini transfusion, that’s the antidote. That is we are calling a transplant.
That’s different than an allogeneic or donor stem cell transplant where there really is transplantation going on. Your immune system is being put to sleep and a new immune system from a sibling or a stranger is put into your body to give you a new immune system. We then task that new immune system with attacking your cancer. For us, that’s a very different ball of yarn.
Chelsey’s Hodgkin lymphoma relapse
Stephanie: Patient Caitlin M. asks, “For relapsed/refractory patients, are there other options aside from chemo to get into remission before a stem cell transplant?”
Chelsey, you went through immunotherapy, but unlike Caitlin, you didn’t respond. After three cycles, your PET scan showed disease progression. I can’t imagine what that was like.
It would be great to understand more about your experience in terms of the conversation you were having with your doctor ahead of the transplant. Are there questions you wish you’d ask your doctor?
Chelsey: I relapsed in the latter part of 2019. I switched to the Mayo Clinic for my care. I had been researching through the relapsed/refractory Hodgkin’s groups on Facebook. I saw nivolumab, brentuximab, and all of those things, and they were a lot less harsh.
I asked about it when I went there and it was a newer thing at that time. My oncologist said, “Yeah, we can give it a try. It’s had really good results.”
Sam mentioned that the side effects of ICE and the side effects of brentuximab are a night-and-day difference. I don’t think anybody wouldn’t want to try the less harsh one leading up to the transplant.
I had three of those treatments, had a scan, and my cancer progressed. My oncologist was honestly shocked as well that it didn’t respond whatsoever and that made me actually ineligible for maintenance, like what Sam had.
We switched to ICE. ICE was the first chemo where I had to be inpatient for three days every time. It was intense.
When your hair falls out on ABVD, for the most part, it’s slowly coming out. With ICE, it was clumps of hair coming out. I was very sick. It was very, very harsh chemo.
Chemotherapy & immunotherapy pre-transplant
Stephanie: Dr. Matasar, for relapsed/refractory patients, can you explain this combination of chemo and immunotherapy in the context of a transplant, hopefully, what this might lead to?
Dr. Matasar: Up until now, the goal for patients who have their disease come back despite good first treatment is to get their disease into remission and then into a round of high-dose therapy or autologous transplant in an attempt to maximize the chances of cure.
Can we cure people reliably and consistently without a transplant by leveraging these immunotherapies either alone or in combination with chemotherapy? This remains a clinical trial-type question; this is not a DIY thing.
My hope for the future is to use these treatments, particularly immunotherapies, to really limit our need to take people through the rigors of high-dose chemotherapy, cure more people, and cause fewer problems.
Determining the sequence of treatment
Stephanie: If the ABVD didn’t work, there’s a relapsed/refractory situation. Maybe there’s some radiation that’s been involved. You have studies about brentuximab, nivolumab, or pembrolizumab alone or in combination. How are doctors having that conversation about the right thing to do next? What is the most promising next course of option?
Dr. Matasar: This is the art standing next to the science. There is some artistry to what we try to do to figure out the right lid for each pot and how to help a patient navigate the course of their illness.
There is no one-size-fits-all anymore. It used to be ICE; that’s all we did. It worked well and it was awful. Now we have a range of choices.
You have to sit with a patient and think through it. How much disease is there that I’m trying to shrink away? How quickly is it growing? How do you feel? How sick is it making you? How quickly do we need to get you better? What was your first treatment? How well did it work? How badly did it not work?
Take all of these factors, try to cram it into your doctorly brain, and try to give some reasonable recommendations. Sometimes you’re going to be as gentle as brentuximab all by itself. Sometimes you’ll want to give more chemo. Sometimes you want to give checkpoint inhibitors alone or with BV. Sometimes you want to do checkpoint inhibitors plus chemo. These are all reasonable courses.
Ideally, what you’re doing as a doctor is working with your patient as a person, as an individual, and charting a course that makes sense for them, for their illness, and for their life.
Stephanie: It’s a really thoughtful response. Are some of the considerations the treatments you had before, how successful they were, what’s already been done… What about things like age or comorbidities or those kinds of factors?
Dr. Matasar: We try not to be ageist, but, truthfully, taking care of a 30-year-old is different than taking care of a 90-year-old and to not recognize that would be silly.
That being said, it’s always a matter of individualization — understanding an individual person’s goals, their preferences, what risks they’re willing to take, what matters to them, and then trying to figure out the best treatment for that person, given everything you know about them, about their value system, and about their goals of care.
Stephanie: Wonderful. I wish every doctor thought like you.
Long-term post-treatment side effects
Stephanie: We’ve talked a little bit about long-term or late-term side effects. Patient Ariadne J. asks, “What is known about long-term post-treatment side effects?”
Sam: I love this question because now I can plug survivorship, which is basically my newfound life passion as a patient-doctor. Cancer survivorship, even though a lot of people don’t necessarily identify with the word survivor, is an important thing to keep your finger on the pulse.
Survivorship applies to this area of medicine that’s changing and evolving. It’s anybody living after a cancer diagnosis and that could be during treatment if you’re on long-term treatment and that could be after your treatment is over.
There are a lot of ways that the cancer experience, even if the treatment goes perfectly, makes you question your life when you’re in your 30s and have your fertility changed. There are all these things that get impacted once you hear that big C word.
Survivorship is an evolving area in medicine that is trying to address all of that. For me, there was a lot. There was identity. There was this existential crisis. Death and dying and making sense of all of that.
The steroids and the other medicine that I had to take impacted my thinking and my emotions. I’m usually a pretty balanced, even person so that was a very hard roller coaster.
There’s some cardiac stuff for some people. Doxorubicin, which is part of the initial treatment, is something that we really need to be thinking about. We’re giving people this medicine that’s toxic to the heart in their 20s, 30s, and 40s. We need to talk about intensive lifestyle interventions like a healthy diet and cardiovascular exercise.
An overall program that focuses on wellness is hugely important in managing long-term side effects and integrative medicine. I’m doing an integrative medicine fellowship. I’m trying to unify everything that I learned in medical school with everything I needed as a patient to get better from cancer and cancer treatment and hoping to offer that to other people.
Those are practitioners that you could consider going to or looking up. Make sure that you communicate everything you’re trying and doing with all of the people who are in charge of your care, including yourself. You’re an important part of that conversation. Cancer survivorship is important for managing long-term side effects.
Stephanie: Chelsey, what were the long-term side effects for you? You talked about going into menopause, for instance.
Chelsey: The main thing I struggle with that is the most apparent in my everyday life is the cognitive side effects of all the different treatments. I honestly think it was from the extreme stress that I was under for so long.
I was on this job in an insurance company and I had to balance things with legal documents. I know that if I were to go back to that job, I would not be able to do it now and that’s taken me a long time to see that that’s okay. I’m still me and I just have to work with things differently.
I have fatigue a lot of times and joint pain. I often joke that inside, I’m 80 years old but on the outside, I’m in my 30s so it feels like that.
As Sam mentioned, there’s a lot of identity crisis that you have as a cancer patient. Who am I now? What happened to the old me? What can I do?
I really want to encourage people to seek community. Even just hearing from Sam, I’m sure some people will say, “Oh, other people feel like that?” That’s definitely what inspired me to start making art and connecting with others. It can truly make a difference in your long-term mental health in survivorship.
Stephanie: Thank you so much, Chelsey. You capture a lot of that in your artwork.
Stephanie: Dr. Matasar, with the newer therapies that are either just approved or in the pipeline, are we addressing some of these long-term/late-term side effects that hopefully people can avoid even years later after treatment ends?
Dr. Matasar: We are. A lot of the drive to develop these newer treatments has been informed by our understanding of late effects, cancer survivorship, and the risks that survivors of Hodgkin lymphoma treated with more traditional treatments go on to face.
We still need to follow with these newer treatments to watch for the possibility of late effects. We don’t believe that they’re going to cause as many or as severe, but part of the work of survivorship is learning from our survivors and walking that path with them as we see how their lives unfold over the years and decades to come.
The number one thing that I would encourage survivors to do is to work with your care teams on developing a survivorship care plan. It can be a paper document or a digital document. It should be something that lives with you that says what your diagnosis was, what your treatments were, and what our understanding is of what you can be doing to safeguard your health in the years to come.
That’s informed by understanding the possible long-term consequences of the treatments that you received, how doctors think you’re best served by taking care of yourself, and what doctors can do to prevent or reduce the risk of those problems as you go on to live your lives.
Stephanie: Wonderful. That’s a great tip. It’s great that the trend of more focus on survivorship after treatment is going to do wonders for so many people.
Shared treatment decision-making
Stephanie: We all want to be more empowered in our care to be able to ask doctors the questions, to feel that we can, and to ask ones that will be impactful.
Dr. Matasar, you talked about how the right treatment for each patient depends on different things like age, health, transplant eligibility, and goals of therapy. How can a patient find out the best treatment options for them and in what order? From a doctor’s perspective, what should that conversation be to elicit the best response for patients and their family members?
Dr. Matasar: I was really disheartened, Chelsey, to hear your story of your doctor disparagingly calling you Dr. Google. Nobody should have to deal with this stuff anymore. We’ve got to be better than that.
Everybody should be empowered to come into a conversation with a doctor as an equal partner in this process. I tell my patients, “This is about you. It’s not about me. I’ve got no ego in this. This is your mountain that you’re climbing. I’m not climbing the mountain. I’m the Sherpa. I’m dragging your bags alongside you. But this is your climb and I’m here to help.”
As patients or as caregivers, if you aren’t feeling valued and heard, then you may not have found the right fit for you in terms of your care team. Everybody should always feel free to be getting a second opinion. I Not enough people take advantage of this sometimes. They don’t want to insult their doctor. I don’t want to be that guy or that gal and I don’t want to be a pain in the ass. Be a pain in the ass.
I like nothing more than when my patients are pains in the ass and they come in with lots of questions. It means they’re doing their homework and they’re really invested. They want to learn and take advantage of whatever I’ve got up in my brain. I love nothing more and any doctor should love nothing more than a patient who’s all in on partnering with me on making this thing work.
Be vocal. Do your research if you want to. You don’t have to. You shouldn’t have to. But if you want to and if it’s something that you value, then that should be celebrated by your care team and never put down.
Chelsey: Have open discussions with your oncologist. If you do find other studies or other treatments, they should be open to answering your questions about it and not being dismissive, even if it’s not an option for you. They should be able to explain to you why or why not.
If you’re a young person about to have a transplant, even if you’re not but if you’re in childbearing age, please ask about fertility. I’m now in menopause at 33 years old.
It was explained to me and I understood. We didn’t really have time to waste to get me to transplant. That’s a conversation you should bring up not only when you’re going into a transplant but also when you first get diagnosed with cancer.
Stephanie: Thank you, Chelsey, those are very important questions. I was lucky to have first-line treatment and be okay, but I asked that question before my intensive chemotherapy. It’s great whenever we’re reminded: advocate for yourself depending on what you want your life to look like.
Finding a Hodgkin lymphoma specialist
Stephanie: Dr. Matasar, it’s clear that for relapsed/refractory patients, and if people are experiencing multiple relapses, it’s hard to find one answer from one doctor. They seek different opinions or get different responses. It’s a very personal discussion to be had.
Is there a right time to find a Hodgkin lymphoma specialist? When should that happen? How can you have that conversation?
Dr. Matasar: It’s tough because it’s very personal. My general philosophy is that people deserve to have expertise in their corner. I also recognize that people want to receive care close to home and they should be able to receive good care close to home.
In an ideal world, everybody would have an oncologist who lives close to them and everybody would have access to an expert to support the decision-making and to support the care journey. Sometimes that would be the same person.
If you lived near an expert, perfect. If you don’t have an expert in your neck of the woods and you want it, then you should have the opportunity to seek out that expert as a consultant and as a backup.
That doctor would work collaboratively with your local oncologist as a team to make sure that they’re doing everything to the best of their ability. You have the expert on standby in case things go sideways. In my mind, that’s the ideal.
If patients aren’t comfortable with what they’re hearing, even from me as an expert, go see somebody else. Hear from another set of lips. Get a fresh perspective. Maybe there will be a better fit in terms of that critical doctor-patient relationship.
Any doctor who doesn’t want you to get a second opinion doesn’t deserve to be your first opinion. Find the care that feels right to you. Trust your gut. The importance of the doctor-patient relationship is too great. It’s too critical in a relationship to settle for anything less than the best.
Stephanie: It’s so resonant and it’s powerful to hear from someone like you, Dr. Matasar. If the doctor doesn’t support you getting a second opinion, they’re not worthy of being your first opinion. I really love that.
Final takeaways
Stephanie: If there’s anything else you want to add, what would you really want people to take away from this discussion?
Dr. Matasar: I’m just bringing it back to The Patient Story. What you’re doing, what we’re doing together is where modern medicine should be. We should be building community. We should be sharing experiences and stories and supporting one another.
Every patient’s journey is unique and yet we don’t walk these paths alone. If you can find ways to build community and be supported by various communities, it makes the journey a little bit less painful.
Chelsey: He said it really well. When I went to my second doctor, I felt comfort and care that I hadn’t gotten before. Make sure that you are having a good relationship with your doctor.
A sense of community is very important because a lot of society puts a little bit of an expectation on our shoulders to always be brave, positive, and strong warriors, and not everyone feels that way.
I just want you to know that’s okay. It’s okay to authentically be yourself and talk about the hard parts of cancer, not just the smiling, ringing the bells, and all of that. There’s a lot more to cancer than that. It’s okay for you to feel the way that you feel, however that is.
Sam: Having lots of questions doesn’t make you anxious so it’s okay to have lots of questions and concerns and to look things up. It’s okay to reject that label because you’re just appropriately concerned about your life and the quality of your life.
Some doctors may be more attuned to knowing to ask about what’s really important to you in your life. Some people may be really busy that they forget that. As patients, it’s up to us to tell our doctors what’s really important to us and things that we like doing.
Share with your doctor what’s really important to you. Not only will it help them to know you as a human being, but it will help inform treatment decisions.
There were times during my treatment and I’ve heard from other patients where it felt like to want anything more than not dying was greedy. We’re beyond that now in medicine.
We are in the era of personalization, community, and individualized care within the guidelines of all the new things that are being discovered. It’s not greedy to want to keep exercising to some degree or keep doing your art or whatever defines the quality of life for you.
Tell your doctor what’s important to you. Reject the anxiety label. Let’s shift the focus from mortality to vitality in cancer. It’s so much more than just not dying. It’s the living part.
Stephanie: You both have exemplified that so much. I’m really grateful to have had you, Chelsey, and Dr. Matasar doing your work in research and helping patients and families holistically. Thank you for the work that all three of you are doing as advocates.
The Latest in Breast Cancer with Dr. Lola Fayanju at San Antonio Breast Cancer Symposium (SABCS) 2022
Interviewed by:
Stephanie Chuang
The San Antonio Breast Cancer Symposium (SABCS) provides the latest information in research, prevention, diagnosis, and treatment of breast cancer.
Dr. Oluwadamilola “Lola” Fayanju is the Helen O. Dickens Presidential Associate Professor in the Perelman School of Medicine at the University of Pennsylvania, the Chief of Breast Surgery for the University of Pennsylvania Health System, the Surgical Director of the Rena Rowan Breast Center in the Abramson Cancer Center, and an innovation faculty member at the Penn Center for Cancer Care Innovation (PC3I).
Dr. Fayanju’s focus as an academic breast surgical oncologist is on health disparities, patient-reported outcomes (PROs), and aggressive breast cancer variants.
Dr. Fayanju sat down with The Patient Story to discuss some of the latest news coming out of SABCS 2022.
discusses breast cancer, PROs, the language used around racial health disparities, and the importance of conferences like SABCS.
This interview has been edited for clarity. This is not medical advice. Please consult with your healthcare provider for treatment decisions.
Introduction to Dr. Fayanju
Dr. Fayanju: I’ve always been interested in women’s health. [I was] one of those kids who always wanted to be a doctor and actually was really leaning towards OB-GYN. [I] was always interested in women’s reproductive rights.
Then when you go to medical school, you find out which parts of the body kind of attract you more. I have to admit, I was actually really attracted to surgical disease, found myself really gravitating towards surgical disease, and really got interested in general surgery.
As often happens, you are drawn into things because of the patients who move you and the mentors who inspire you. I was really moved by a patient who was a lot like me when I was a third-year medical student. She was about my age. She was actually also Nigerian.
She was presenting with a large triple-negative breast cancer, and she was alone. She had no family in the United States. I actually remember her starting to cry as I was examining her. I was seeing her in a safety net clinic. That is a clinic that was staffed primarily by trainees overseen by altruistic attendings at my medical school, who then connected those patients to tertiary care.
[I had] a wonderful couple of mentors, including Julie Margenthaler, who is the Chief of Breast Surgery at Washington University, and Ira Kodner, who was a colorectal surgeon but became very famous in the world of medical ethics, as well as care for the underserved.
Working with them, [I came] to realize that patients who presented through the safety net clinics were more likely to present with delayed care and more likely to present with a more advanced stage. That really launched, I would say, my career as a health services researcher and as someone interested in care that really reflected disparities in our society and our ability to provide equitable care.
I became interested in surgery because of the disease, I became interested in breast cancer because of the patients, [and] I also became inspired by having great mentors.
It all seems very linear, finding myself here now as a breast surgeon, but it was actually multifactorial and looks more clean and neat than it felt in the moment. But here I am today with the privilege of being a breast surgeon.
How did you feel meeting that patient who had delayed care?
I felt anger. I felt frustration. I felt the beginnings of despair, but then held myself back, thinking, “How could I make a difference?” Her experience and my experience working with the safety net clinic there actually led to a research project.
What was exciting about that [research project] is that it actually led to a change in the way that care was provided in St. Louis. It used to be the case that patients who were seen in one of the clinics that were treating patients who had no healthcare or who are underinsured — those patients often had to go back to their primary care providers to get referred to the tertiary clinic to get cancer care.
In fact, through research that we conducted, we were able to demonstrate that this led to delays because of having to redo imaging [and] because of missed appointments. It led to a change through the St. Louis Health Commission in the way that care is provided for these patients.
For me, it was a way to show that research didn’t have to be something that was localized to the ivory tower. It could actually be impactful. It could actually translate into policy and into real-world effectiveness. That was really exciting for me.
The importance of SABCS and other conferences
The importance of conferences like San Antonio, ASCO, ACR, or Society of Surgical Oncology is that we who are engaged in the scientific process take what we learn and implement it in our everyday care.
The tragedy of it is that often it takes too long. We know that the average amount of time it takes for our innovation to be implemented in routine clinical care is about 9 years.
One of the things that are really exciting [is] the field of implementation science, which at my institution, Penn Medicine’s Abramson Cancer Center, we actually have a funded implementation science center, which I’m a part [of].
That works to bridge the disconnect between discovery and delivery to ensure that what is found, what is discovered, and what is innovated by scientists actually makes it to patients.
What I would say is important about San Antonio is one, announcing new medications, devices, or approaches to care that will make a difference in the lives of patients with breast cancer. Two, updates on trials that were announced in the past that we now know more about. Then, three, ways in which we can take knowledge that has been kind of assumed to be standard and how we can actually apply that and update that in regular practice.
[Here are] examples of each of those 3 things. One, we are increasingly weighing the results of trials that will tell us how best to manage HER2-low disease. That is patients who have some HER2 expression, but where they don’t rise [to] the level of expression that we used to think was needed to benefit from targeted therapy.
An example of the middle one is the reporting of our understanding of Oncotype DX as both a prognostic and predictive tool for helping us better treat patients with estrogen-receptor-positive disease.
Then a third example is a talk that I’m giving today as part of a panel on patient-reported outcomes. [PROs] are opportunities for patients to describe how they’re feeling, what symptoms they’re experiencing, [and] what psychosocial challenges they might have that might prevent them from optimizing their breast cancer journey.
Those are 3 ways in which conferences like this allow us to communicate new findings, update knowledge we already have, and translate information and approaches we have into the clinical realm for the benefit of patients. Those are some examples of why San Antonio is important.
HER2-low breast cancer
The way to think about it is we’re looking for more opportunities for treatments. I think of HER2 targeted therapy as really an ideal within oncology because it really has changed our ability to achieve pathologic complete response — that is, eradication of tumor prior to surgery just through the use of systemic therapy.
It really has represented a gold standard that we’re trying to achieve for other types of molecular subtypes. Really, [what] we’re trying to figure out more and more is which types of HER2-low can be treated with systemic therapy. In whom can we deescalate other types of treatment? We know that some of the targeted therapy is very hard on the body, and so that’s something that we’re hoping to learn more about.
What are the new emerging treatments for breast cancer?
One of the big trials that came out several years ago was TAILORx, which allowed us to understand how well Oncotype DX, which is a genomic test that allows us to understand whether or not women with estrogen-receptor-positive breast cancer would benefit from chemotherapy in addition to endocrine therapy in the adjuvant — that is, post-operative setting.
Yesterday, an update on that was provided. It was very important in that it showed that women who had low or intermediate-risk Oncotype scores did not benefit substantially from additional chemotherapy beyond just getting endocrine therapy, except for women who were 50 years or younger. If they had an intermediate risk score, those individuals had some potential benefit from getting chemotherapy.
Worse outcomes reported for people of color
What was an unfortunate finding within the study was that Black women had worse outcomes even when you controlled for other factors. The way that was communicated was, I think, in a way that unfortunately is often communicated when trials are described.
Black race was communicated as an adverse factor, which is really not the way in which we want to describe these types of outcomes in minoritized groups. We know that race is a social construct.
As Dr. Lori Peirce, a very prominent radiation oncologist at the University of Michigan and former president of ASCO, described immediately before that presentation, race is a social construct that nonetheless has power and it is notable that in African Americans for many years, there was the one-drop rule in effect.
It was used to justify the enslavement of children of miscegenation in order to keep those children enslaved. It is also used to withhold rights from people of Native American ancestry by having it be that you have to have a certain minimal amount in order to claim Native American ancestry and take advantage of certain rights that are ascribed to them through the U.S. government.
Again, the use of ancestry is often political; it is not biological. When we ascribe risk or we describe disparities that are observed in certain groups, we need to really tease apart when we’re talking about genetic ancestry and when we’re talking about the systemic racism, bias, and the structures that contribute to seeing untoward outcomes in those groups. That, unfortunately, was not really described in the relaying of those results.
Language around racial disparities in healthcare
\We should never use language that Black race is an adverse factor or Hispanic ethnicity is an adverse factor. People’s identity is not an adverse factor, even if we find disparate results in that group.
The way I would describe those results is to say that, unfortunately, we continue to find worse outcomes amongst Black women. This is an important subject of future inquiry that hopefully will be better understood if we deliberately target Black women for enrollment in these trials, as they continue to be under-included and underrepresented in clinical trials.
Why is there a lack of diversity in clinical trials?
Many of the women who choose not to participate in clinical trials, who are African American, it’s not because they can’t afford to do so. It’s that they have a justified mistrust in the system, a system that has not earned the trustworthiness of people of color.
I think that descriptions of trial results matter. Words matter. As clinical trialists [and] as scientists, we need to think about how the words we put out there will influence [the] future behavior of the people we’re trying to attract to science.
Patient-reported outcomes
Dr. Fayanju: Patient-reported outcomes allow patients to communicate their feelings, sensations, [and] experience without the filter of the physician’s perspective. We know through some landmark work that it may actually improve survival, being able to communicate those experiences directly to their clinicians in a timely fashion.
We also know it is associated with improved shared decision-making, and improved quality of life. In vulnerable populations, it may even allow us to anticipate potential delays in receipt of care and receipt of treatment.
The difficulty is that there’s already a lot of pressure on the patient encounter with regard to what patients are trying to communicate and what doctors are trying to achieve. It’s not that doctors or clinicians as a whole aren’t trying to hear what their patients are trying to say. It’s often you have 15 to 30 minutes to accomplish all of those things.
What I’m hoping to communicate is how best to do that. What are some strategies for collecting that data prior to the patient encounter, during the patient encounter, and potentially afterward? Does it have to be limited to the cancer setting? Are there ways in which we can potentially engage primary care?
Additionally, what are the modalities in which we need to engage patients? How can we it feel less like work? One of the things that we need to think about is how to engage behavioral economics to make it feel easy, both for clinicians and patients. We need to make this not feel like homework, both for patients and for providers.
How can the patient-doctor experience be improved?
We need to be multifaceted. We need to recognize that our patients don’t all engage with patient portals. Many of them have smartphones, but levels of comfort vary. We also don’t want to exacerbate existing disparities by giving some patients a lot of opportunity to communicate with us and other patients the minimal opportunity to communicate with us.
Being able to use both smartphones and simple phones, being able to take advantage of opportunities to communicate in the waiting room, being able to sometimes rely on paper and pencil, and also making sure that we have culturally humble as well as linguistically diverse opportunities for collecting that data are really important.
Looking forward to future research on breast cancer
I’m really excited about the idea [of] precision oncology, which right now focuses on the kind of molecular milieu.
I think it also needs to think about the social milieu of the patients. How can precision oncology take into account the specifics of a patient’s social context and tailor their care to their lives, not just the cells in their body and the DNA of their tumor?
With the increased attention, the social determinants of health that COVID-19 really caused all of us to really focus on, I hope that there’s more research. I hope it’s sustained interest in making all of us believe that data that’s important to collect, act upon, and incorporate into our sense of what health should look like and how we can promote cures by incorporating the whole human into our care of the patient.
