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Your MPN, Your Journey: How New Discoveries Will Impact Personalized Care

Your MPN, Your Journey: How New Discoveries Will Impact Personalized Care

Whether you’re newly diagnosed or managing ongoing care, learn how the latest findings impact your myeloproliferative neoplasms (MPN) treatment options and quality of life.

Dr. John Mascarenhas of The Tisch Cancer Institute at Mount Sinai and patient advocate Andrew Schorr share the latest breakthroughs in MPN care. Explore personalized treatments, cutting-edge therapies, and groundbreaking research that are changing how MPNs are treated. Learn how new discoveries can improve your treatment options, help manage side effects, and enhance your quality of life.

Your MPN, Your Journey: How New Discoveries Will Impact Personalized Care
Hosted by The Patient Story Team
Dr. John Mascarenhas (Mount Sinai) and patient advocate Andrew Schorr share the latest breakthroughs in MPN care. Explore personalized treatments, cutting-edge therapies, and groundbreaking research that’s changing how MPNs are treated. Learn how new discoveries can improve your treatment options, help manage side effects, and enhance your quality of life.
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Hear about cutting-edge research and new therapies presented at the 2024 American Society of Hematology meeting. Learn how individualized treatments can improve your outcomes and quality of life. Get practical strategies for handling common side effects of MPN treatments. Discover innovative therapies, including JAK inhibitors and combination treatments. Find out how to stay informed and participate in promising clinical trials. Learn the key questions to ask your healthcare team to ensure you’re receiving the best, most current care.


The Leukemia & Lymphoma Society is here for you with information about clinical trials, resources, and support.

Thank you to The Leukemia & Lymphoma Society for their partnership. The Leukemia & Lymphoma Society is here for you with information about clinical trials, resources, and support.


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Thank you to Sobi and Incyte for supporting 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 to make treatment decisions.



Introduction

Tiffany Drummond: As a clinical researcher and patient advocate, I am excited to talk about some very exciting developments in MPN treatment, including important breakthroughs and promising new combination therapies. Many of these advancements were highlighted at the 2024 American Society of Hematology meeting, better known as ASH, where leading doctors and researchers from around the world gather to share the latest findings.

Our goal is to provide patients and care partners with valuable information to help in their healthcare journey. We want to empower you to have informed conversations with your medical team so you can better understand your treatment options and how to balance effective care with maintaining your quality of life.

Tiffany Drummond patient advovate

We want to thank our sponsors, Sobi and Incyte, for their support, which helps us host more of these programs for free to our audience. The Patient Story retains full editorial control over all content as always. We also thank all of our promotional partners for their support. It is because of you our programs reach the audience who needs it. While we hope you find this program helpful, please keep in mind that the information provided is not a substitute for medical advice.

Let’s kick off another engaging conversation with amazing patient advocate Andrew Schorr and leading hematologist-oncologist Dr. John Mascarenhas.

Your MPN, Your Journey: How New Discoveries Will Impact Personalized Care

Andrew Schorr: Welcome to this program about the latest in MPNs. I’m with a friend and leading scientist-physician Dr. John Mascarenhas at The Tisch Cancer Institute at Mount Sinai in New York. John, you have many titles. You’re a noted hematologist and subspecialist in MPNs. Thanks for joining us.

Dr. John Mascarenhas: Andy, thanks for inviting me. I always enjoy connecting with you.

There has been a lot of interest as we understand the disease biology even greater than we did in 2005 when the JAK mutation was first discovered.

Dr. John Mascarenhas

Is There Encouraging Progress for Myelofibrosis Patients?

Andrew: It’s very personal for me. I’ve been living with primary myelofibrosis since 2011 and it’s somewhat progressed. I’ve been on two JAK inhibitors and maybe I’ll switch to a third. Will I have combination therapy with a JAK inhibitor and something else? We all wonder about that.

Some of us are concerned. Should we have a transplant or can medical therapies take the place of a transplant? If you have polycythemia vera or essential thrombocythemia, you ask if you’re going to progress to myelofibrosis and at what rate. How is our situation different from the next person?

John, you were a speaker at the 2024 ASH meeting in San Diego, and you were involved in lots of studies. I want to talk about what’s significant for patients. We have the current therapies and a lot of drugs that many of us have never heard of that are in development. You’re involved in a lot of the development. Which way is the wind blowing? Are you encouraged for us? We saw progress in other blood cancers. Is it now starting to blossom in MPNs, specifically for myelofibrosis?

Dr. Mascarenhas: The short answer is yes, I am encouraged. That’s a fundamental defect that I have, continuing to be optimistic no matter what we’re looking at. That optimism has been maintained over almost 20 years that we continue to move in the right direction, but unfortunately, often not fast enough for our patients.

What I’ve seen is the evolution of the JAK inhibitor era, which you alluded to. We have four JAK inhibitors that are approved that allow us to tailor and personalize the therapy to patients based on their profile and blood counts, and even provide serial sequencing of JAK inhibitors. But that isn’t enough.

Your MPN, Your Journey: How New Discoveries Will Impact Personalized Care

There has been a lot of interest as we understand the disease biology even greater than we did in 2005 when the JAK mutation was first discovered. We now recognize that there’s a greater degree of complexity and heterogeneity among patients. There are a lot of different pathways that appear to be very important and relevant to the physiology and pathophysiology of this disease.

Your MPN, Your Journey: How New Discoveries Will Impact Personalized Care

There is a real interest in targeting the grandfather/grandmother cell in which the disease originated. We are looking for vulnerabilities in those pathways in that cell population that would allow us to ultimately delete that cell to provide deeper responses and even curative approaches. Outside of transplantation, the therapies we have don’t cure patients. They address issues that are not unimportant, like spleen size and cytopenia or low blood counts, and improve how patients do and ultimately prolong survival. But we’re looking to leverage these findings from the lab to find therapies that change the disease course and improve outcomes like survival and progression-free survival.

Your MPN, Your Journey: How New Discoveries Will Impact Personalized Care

Many agents are leading us in that direction. These agents turn on the p53 pathway, like navtemadlin, an oral drug that binds a protein called MDM2 and relieves repression on p53, allowing for the natural cell processes to be induced, which is cell death of the malignant cell. It’s a fascinating concept. Navtemadlin is at the forefront of doing that. We showed data in the relapsed/refractory setting of using that as a single agent. We’re now going to move it up to combinations.

Your MPN, Your Journey: How New Discoveries Will Impact Personalized Care

Drugs like that are telling. They’re hitting pathways that can induce malignant cells at their core to die, to synergize, and be practical with it. We want to create therapies and approaches that capitalize off the benefits we have, like JAK inhibitors, which can be well-tolerated but can provide deeper responses than what we’ve seen thus far. Navtemadlin is a great example of that.

Your MPN, Your Journey: How New Discoveries Will Impact Personalized Care

What Have We Learned from MPN Gene Mutations?

Andrew: We’re going to go through a laundry list as we dig into different drugs, but I want to go over what you said. You’re trying to go back to the very basics of cancer, what went haywire in a patient who ends up with a bone marrow problem that leads to one of the MPNs. Can you shut it down at the earliest stage by understanding it?

Over the last few years, your scientific community has identified different oncogenes (cancer genes) that have been responsible for that. You talked about the heterogeneity or the differences. Some of us have CALR, some have JAK2, and some have MPL. Is that understanding helping?

Your MPN, Your Journey: How New Discoveries Will Impact Personalized Care

Dr. Mascarenhas: I do think it helps because we recognize that it’s not a monolithic disease. The driver mutations and the different amounts of those mutations that are understood to be present in the bone marrow cells as well as the sequence in which the mutations arose all tell a picture. They paint a picture of complexity at the molecular and cellular level that explains why there’s heterogeneity at the clinical level — why some patients have very high white counts and some patients have very low platelet counts; why some patients have very big spleens and some patients have a lot more anemia and transfusion dependence. It can all be explained relative to the biology, these mutations, and the effects of these mutations.

Your MPN, Your Journey: How New Discoveries Will Impact Personalized Care

Once we’ve realized that, the next step is how to take all of that complex data and distill that to help us understand how best to target those cells based on that genomic complexity. That’s where things like artificial intelligence and machine learning will help us move the field forward as it’s doing with other sciences. We’re moving in this direction of a deeper understanding of the biology from the molecular standpoint that informs us with prognostication, which is important, but most importantly, therapeutic implications.

Your MPN, Your Journey: How New Discoveries Will Impact Personalized Care

There is substantial data that would suggest that certain mutations likely influence outcomes and responses to treatment. Most patients will have had next-generation sequencing. You look at these gene panels and see if mutations exist in any given individual and what they mean. We know that some of these mutations can have influenced prognosis and outcome. Some of these mutations and the presence of more than one mutation could even predict a lesser response to drugs like ruxolitinib, a less robust spleen, a shorter duration of response, and a quicker time to failure of drugs. Knowing that upfront may be strategic in understanding how better to approach diseases rather than give the same drug to everybody.

Your MPN, Your Journey: How New Discoveries Will Impact Personalized Care

The same drug for everyone is not going to be the right answer. At the forefront, drugs that target CALR, for example, are exciting. We’re taking out a subset of patients with myelofibrosis and ET with the mutant CALR protein expressed on the surface of the cell and saying these patients may be best served by a drug that specifically targets that protein on the surface. That wouldn’t make sense for a JAK2-mutated patient. A JAK2-mutated patient may be best served with a small molecule inhibitor that specifically and selectively targets the JAK2 mutation, which is under investigation. You’re seeing these mutations inform the clinical development of very selective and specific drugs.

Your MPN, Your Journey: How New Discoveries Will Impact Personalized Care

Andrew: I almost think of next-generation sequencing like a modern art painting with red and blue splattered. Hopefully, with some consultation with an MPN specialist, you can find out how current therapies or investigational ones apply to your specific situation.

The genes that are driving our illness may evolve, so what the story is today may not be the same story in a year, two, or three.

Andrew Schorr

How Do Doctors Choose the Right JAK Inhibitor for the Patient?

Andrew: You also mentioned how the genes that are driving our illness may evolve, so what the story is today may not be the same story in a year, two, or three. I’ve been living with myelofibrosis since 2011. It has been pretty stable and has been driven by JAK2 V617F. You mentioned the four current approved JAK inhibitors. They have nuances and it would seem like the choice of which one or sequencing, as you said, may vary by patient based on their situation. How do you know where to start?

Your MPN, Your Journey: How New Discoveries Will Impact Personalized Care

Dr. Mascarenhas: We are blessed that we have choices today because it wasn’t always the case. We have opportunities to select drugs that may be best suited for different subsets of patients. For example, patients with low platelets or those who have cytopenic profiles may be best served by drugs that are easily delivered and have rationale in that patient population, namely pacritinib over ruxolitinib, in which we know platelets often limit the ability to dose up on ruxolitinib. Fedratinib, even more recently, had some data providing some more security there. We know that platelets could be a determinant of which one of the JAK inhibitors you’re going to select.

Most patients will start with ruxolitinib. It’s the oldest, most familiar, and probably still one of the best drugs that I’ve ever seen in this field

Dr. John Mascarenhas

Anemia is another one that’s gotten a lot of attention. It can be a major issue for patients at presentation and can worsen over time. Ruxolitinib is a great drug, but it can worsen anemia for some patients, so it may not be the best therapy in that setting. However, drugs like momelotinib or even pacritinib that inhibit ACVR1, a different protein, can improve anemia in some patients.

Your MPN, Your Journey: How New Discoveries Will Impact Personalized Care

We use patient profiles to help us understand which drugs to choose from, but for the most part, most patients will start with ruxolitinib. It’s the oldest, most familiar, and probably still one of the best drugs that I’ve ever seen in this field in terms of achieving its goals. But again, not every patient fits the bill, so you can tweak that as needed.

Is Combination Therapy the Next Step in Building on JAK Inhibitors?

Andrew: A lot of studies talk about building on ruxolitinib and I’m sure there’s discussion about building on the other JAK inhibitors as well. Is a one-two punch necessarily better? Is that where you’re headed?

Dr. Mascarenhas: It’s definitely what we’re interested in asking. We have JAK inhibitors that are disposable and beneficial, but they’re not sufficient. We have other drugs that have demonstrated clinical activity and are rational and validated in preclinical models, which are systems that help us understand whether it makes sense to take it into a patient. These are drugs like pelabresib, imetelstat, navtemadlin, and selinexor, but each drug has a rationale and is active even as a single agent in these diseases.

Your MPN, Your Journey: How New Discoveries Will Impact Personalized Care

The question being asked now is: is it better to combine the two drugs? If you look throughout oncology, most of oncology is treated with combinations of therapy. It’s very rare to find an oncologic disease, whether it’s of the blood or of the solid malignancy, where we use one agent and then if it fails, we go to a single subsequent agent. Usually, combinations of therapy are more potent together.

If you put agent X — whether it’s selinexor, navtemadlin, pelabresib, or imetelstat — together with ruxolitinib, which tends to be the first drug you pick, you tend to see better efficacy and, in some cases, even better safety profile when the two are combined.

Dr. John Mascarenhas

A term we often use is synergize. If you take either drug alone in a lab and expose them to malignant cells, the combination of the two drugs works better than one plus one — it’s almost one plus one plus one. You get better effects in terms of killing or limiting malignant cells. We hope to replicate in humans what we see in the lab or in mice that are engineered to have these diseases.

Your MPN, Your Journey: How New Discoveries Will Impact Personalized Care

The data in the field has taken us towards the route of combining novel agents that have shown activity in the relapsed/refractory setting with a single agent as combination therapy upfront. Most of the data would point that if you put agent X — whether it’s selinexor, navtemadlin, pelabresib, or imetelstat — together with ruxolitinib, which tends to be the first drug you pick, you tend to see better efficacy and, in some cases, even better safety profile when the two are combined. The natural question is: if we take two active agents, can we get deeper responses? What does deeper response mean?

Your MPN, Your Journey: How New Discoveries Will Impact Personalized Care

At the most superficial, it could mean more spleen reduction — that’s a regulatory endpoint — and deeper symptom improvements, but we’re looking at other biomarkers to understand if we’re hitting the target that we want. Are we getting deeper reductions in the driver mutation amounts of the variant allele frequency (VAF)? Are we reducing those numbers to suggest that we’re reducing the burden of disease in the bone marrow? Since we can’t measure it with a CT scan, are we reducing the disease in the bone marrow from other viewpoints like fibrosis? Is the amount of circulating abnormal cells reduced, something called the CD34+ cell number? Are we also reducing cytokines or inflammatory markers to a deeper extent?

Your MPN, Your Journey: How New Discoveries Will Impact Personalized Care

We look at all of these biological aspects and hallmarks of the disease. Are we getting even more profound effects on these biomarkers, suggesting that we’re modulating the disease more effectively? At the end of the day, MPN patients want to live better and longer, but we look for markers early in trials to understand if we’re getting there.

Andrew: These are very powerful medicines. Will the quality of life be diminished if you add this other big gun? We want to live longer, for sure, but we want to live well. Could you talk about the power of the combinations but the worry about additional side effects?

Your MPN, Your Journey: How New Discoveries Will Impact Personalized Care

Dr. Mascarenhas: I’ll give you a prime example where one plus one can equal three from an efficacy standpoint but might still equal one from a safety standpoint. A great example is the MANIFEST-2 study. We took JAK inhibitor-naive patients with myelofibrosis and randomized them to the standard of care, which would be ruxolitinib, plus a placebo and ruxolitinib plus the study drug pelabresib, which is an oral BET inhibitor, a very rational drug that modeling has shown us should synergize very nicely with ruxolitinib. It’s a double-blinded study, so the patients and investigators don’t know what the person is getting; only a computer knows.

The answer is it did. Efficacy-wise, if you look at 24 weeks, there were very profound reductions in spleen size and very profound reductions in symptoms. If you look at the biomarkers — the bone marrow fibrosis, the inflammatory cytokines, and the JAK2 mutation — the reductions were far more significant. Everything aligned with the superiority of the combination.

Your MPN, Your Journey - How New Discoveries Will Impact Personalized Care

But most intriguingly, if you looked at the safety profile, there were fewer grade 3 and 4 treatment-emergent side effects with the combination than with the single agent. I’ve never seen that before where two active agents combined got almost double the clinical activity and less toxicity. I hope it’s reassuring for patients that double the action doesn’t mean double the trouble. You can combine some of these drugs, get good activity, and not make patients feel worse but even make patients feel better and have less toxicity.

Your MPN, Your Journey - How New Discoveries Will Impact Personalized Care

We have to acknowledge that we add toxicity sometimes when we add combinations. Sometimes that toxicity is in the form of gastrointestinal (GI) toxicity or lower blood counts. Sometimes it’s a trade-off. Are we getting deeper responses that could lead to better outcomes where we could be getting more cytopenia and more need for monitoring, or even transfusions? Is that reasonable for a given individual? Could we be adding some nausea and diarrhea by doing that?

What’s key to this conversation is: are we adding these toxicities continuously or periodically when some of these (MPN treatments) are dosed? For example, navtemadlin is a very active drug. When we looked at the data, it was very clear that you could get some GI toxicity. It was mostly low-grade and easy to manage, but it’s there. The drug is dosed for seven days in a row out of 28 days. The toxicity was mostly relegated to days two and nine.

Your MPN, Your Journey - How New Discoveries Will Impact Personalized Care

This is an esoteric or personal question: for any given individual, if that deeper response could lead to better outcomes, is that period where you may have GI toxicity worth it? From a human perspective, I’m not sure. From a clinical investigation, we’re interested in trying to understand: are we providing full good at a price or is it going to be good and no price? Nothing comes for free, but these are important questions.

We rely on the patient community to tell us. We don’t simply ask patients how they’re feeling. There’s also a much-validated tool that we use called Patient Global Impression of Change (PGIC), which is simple. It asks: if you put everything together, all the toxicities that might ensue and benefits that you’re noticing or being told by the physician that you’re getting, do you feel like you are the same, a little better, a lot better, a hell of a lot better, or a little worse? The PGIC is a very valuable tool because patients will tell you if the whole thing is worth it or not. It’s key to making sure that globally, they believe that they feel that what they’re doing and what they’re going through is a net benefit at the end of the day.

Your MPN, Your Journey - How New Discoveries Will Impact Personalized Care

Transplant vs. Medication: Where Do We Stand?

Andrew: You’ve mentioned a number of these drugs that are investigational on top of the four approved JAK inhibitors. I’m 74, so I don’t plan to do a transplant, but some patients are younger and it’s been recommended they have a transplant. As you say, it can be curative. It’s a big gun. I lived in Seattle for a long time where they developed it originally and I knew about the morbidity and mortality, and that continues for some people. Where are we now with transplant versus all these other treatments?

My hope and my goal in my lifetime and my career would be that we ultimately develop therapies that make transplants unnecessary.

Dr. John Mascarenhas

Dr. Mascarenhas: Fortunately or unfortunately, transplant remains the only modality that we have for a cure and, as you’ve pointed out, it’s not for everybody. If you’re advanced in age or have too many comorbidities, a transplant may be more dangerous and detrimental than it ever will be helpful. I’m an advocate for transplant, but it’s for a select group of patients. Patients who go into transplant are moving into an aggressive type of therapy, but it has to meet the aggressive nature of the disease. You would never take someone who has a low-risk version of the disease right into transplant because you could cause more harm earlier on than good.

It’s a complicated discussion that involves understanding where the patient is from a disease perspective, the nature of their disease, their goals, understandings, and expectations, and making sure they have a donor and support system to do a transplant. I encourage that conversation. It’s important, but it’s not going to be for everyone.

Your MPN, Your Journey - How New Discoveries Will Impact Personalized Care

My hope and my goal in my lifetime and my career would be that we ultimately develop therapies that make transplants unnecessary. At its core, transplant is taking immune cells and using them to ultimately get rid of the grandfather or grandmother cell, which is what we call the stem cell that started the disease process, and that’s an immune-mediated elimination of the cell. If we can figure out how best to do that with medicinal therapies that may not be as intense, then we could get to a point where transplant may become historic.

Your MPN, Your Journey - How New Discoveries Will Impact Personalized Care

At Mount Sinai, that’s what a lot of our translational research has been based on, and Ron Hoffman and others have taught me this. It’s a stem cell-directed approach to shut down or eliminate that pool of cells that allows the disease to persist. Even after you wipe out cells with a transplant, those cells can come back. Using science and collaborating with patients, targeting stem cells with rational therapies is the only way we’re going to do that.

Your MPN, Your Journey - How New Discoveries Will Impact Personalized Care

If it weren’t for patients who show up at tertiary care centers like ours, meet physicians like me, and sign consent forms to allow us to take their blood, bank it, and use it to understand the biology, then we wouldn’t be able to move the field forward. It’s the science that we derive from our patient’s cells and their generosity, and allowing us access to their data that help us understand how to make the next generation of therapies that will target that stem cell.

Andrew: I’m a big believer in that. I go to a tertiary center as well. I’m willing to give the blood and I’d recommend that to people.

Your MPN, Your Journey - How New Discoveries Will Impact Personalized Care

Will PV or ET Progress to Myelofibrosis? What Can Be Done?

Andrew: We have people who may not have myelofibrosis. They may have polycythemia vera or essential thrombocythemia. As they learn, they know that there can be a progression from one to another. They’re not on a JAK inhibitor, but they might be someday. What do we know about slowing progression or even knowing who will progress?

Dr. Mascarenhas: We know that the disease is chronic and progressive. Progression is not just a fear of the patient; it’s a reality that we as physicians try to risk stratify. When we meet patients, we try to understand if there are risk variables that may help us predict what that timeline might be to make treatment decisions.

Your MPN, Your Journey - How New Discoveries Will Impact Personalized Care

We believe the rate of progression and the reason patients progress is due to clonal evolution. Blood cells acquire more mutations and alterations that allow that cell population to behave differently and change the clinical picture. We use variables, like age, anemia, white blood cell count elevation, presence of circulating blasts, low platelet count, and high molecular mutations or chromosomal abnormalities, and enter them into prognostic scoring systems, which can be found online.

Many patients will find one of these prognostic scoring systems, plug their information in, and get a sense of where they fall in prognosis. But I will caution patients: if you ever do that or speak to a physician, you must understand statistics. Please don’t make the mistake of assuming that the median survival you see is what your lifespan is. It doesn’t work that way. It’s a framework to understand where in the spectrum of patients you fall and help us make treatment decisions about the most appropriate therapy.

Your MPN, Your Journey - How New Discoveries Will Impact Personalized Care

Our approach will evolve over time to a more refined, risk-adapted approach where we use mutations to guide us not just in the selection of therapies but the timing of when to use those therapies. From seeing enough patients, I understand that progression is a real concern for ET, PV, and myelofibrosis patients.

Your MPN, Your Journey - How New Discoveries Will Impact Personalized Care

Progression to Acute Myeloid Leukemia (AML)

Dr. Mascarenhas: The ultimate concern about progression is the potential to evolve into acute myeloid leukemia (AML). Sometimes you might hear it called the blast phase. That’s an aggressive form of leukemia that is problematic and is a fear factor for patients and physicians treating patients with MPNs.

To see if that’s a concern, we look at mutations like p53, a type of mutation, or the presence of circulating blasts or blasts, which are immature cells in the bone marrow. That information can help us get a sense of what the risk may be of a patient transforming into an acute myeloid leukemia.

MPN-related AML is molecularly distinct from de novo AML… Unfortunately, it’s often more resistant or refractory to the traditional types of therapies that we give in that setting.

Dr. John Mascarenhas

Are We Making Progress with Secondary AML in MPN Patients?

Andrew: There’s a percentage of MF patients who traditionally would progress to AML. There’s been progress in what you’d call primary AML and there have been a number of drugs developed, but secondary AML that would come out of myelofibrosis, I understand, has been more difficult. Where are we with that now?

Dr. Mascarenhas: You’re right. For what we call de novo AML, we have a plethora of different agents. They’re still not enough, but we have agents that can be quite effective in trying to control that type of AML and induce a response. Those agents typically are not as effective and don’t have a very significant impact on the disease process in secondary AML or AML that arises out of an antecedent myeloproliferative neoplasm, whether that’s ET, PV, or myelofibrosis.

MPN-related AML is molecularly distinct from de novo AML. It looks different from a mutation profile and behaves differently. Unfortunately, it’s often more resistant or refractory to the traditional types of therapies that we give in that setting. There’s no benefit to an AML patient who had an MPN previously by giving them induction chemotherapy unless that’s followed by a transplant. Every study tells us that doesn’t improve patient outcomes, so we know that’s not effective.

Your MPN, Your Journey - How New Discoveries Will Impact Personalized Care

We rely on drugs like hypomethylating agents, like decitabine, decitabine+cedazuridine, or azacitidine. These epigenetic therapies try to induce maturation of these immature cells, which is what leukemia is, or immature cells that don’t know grow up. We try to induce that maturation process so that they die a more natural death. It’s less intense, but it’s more effective with this type of AML.

Your MPN, Your Journey - How New Discoveries Will Impact Personalized Care

There are a lot of other therapies under clinical investigation. Some of them are molecularly directed therapies. We’ve run trials with IDH inhibitors, oral drugs that specifically go after mutations that can be present in AML that arose out of an MPN, which can be quite effective. Understanding the molecular profile of that AML could inform treatment decisions. The reality is that’s an AML that’s problematic. Our real goal is to stop the process from evolving to AML because we know that treating that is complicated.

Your MPN, Your Journey - How New Discoveries Will Impact Personalized Care

Role of Interferon for the Treatment of MPNs

Andrew: We’ve had interferon for a long time. Where does that fall in?

Dr. Mascarenhas: Interferon, which is a biologic that has been around a long time, is an interesting compound. There is a lot of data in the lab and in patients who’ve been treated on trials, particularly polycythemia vera and essential thrombocythemia, that this drug can be anti-cloning. You can see changes in blood count numbers with ET and PV, and reductions in mutation levels that are driving mutations like the JAK2 mutation. Groups have shown that a reduction in those levels correlates with better event-free survival (EFS). Events are clotting, bleeding, progression, and death in ET and PV. We see the value in that setting. Interferon’s increasing in its utility and use throughout the world.

Your MPN, Your Journey - How New Discoveries Will Impact Personalized Care

Myelofibrosis is a little bit different. There’s probably some value there, particularly in treatment-naive early forms of the disease or prefibrotic forms. Interferon is under active clinical investigation in a global study, which is taking patients with lower-risk diseases that don’t have so much complexity and fibrosis in their bone marrow and have seen so many different types of therapies. Interferon works best early on in the disease course. Once the disease gets too complicated and too advanced, it may not be that effective.

Your MPN, Your Journey - How New Discoveries Will Impact Personalized Care

New Drugs Being Studied in MPN Treatments Clinical Trials

Andrew: We mentioned the ASH conference. There are the European Hematology Association (EHA) meetings and other meetings that you attend as well. You mentioned selinexor and navtemadlin. There’s nuvisertib, elritercept, and DISC-071, an anti-hemojuvelin antibody. Help us understand this constellation of what’s going on.

Dr. Mascarenhas: You’ll notice certain themes. For the uninitiated, these names are somewhat frustrating because they don’t resonate. If one were to think about themes, they make sense.

What we’re trying to do in translating the understanding of the biology from the laboratory to the clinic is targeting signaling pathways. These pathways are inappropriately activated in malignant cells that continue to tell them to proliferate, secrete inflammation, and do things that they’re not supposed to do.

Your MPN, Your Journey - How New Discoveries Will Impact Personalized Care

We have very intricate, complex, and overlapping signaling pathways in many malignancies, including myelofibrosis. Multiple signaling pathways are inappropriately activated or hyperactivated. For example, JAK inhibitors inhibit the JAK-STAT signaling pathway and you’ll notice those drugs end with “nib.” Those are small molecule inhibitors that inhibit enzymes in those signaling pathways.

Your MPN, Your Journey - How New Discoveries Will Impact Personalized Care

Nuvisertib is a small molecule inhibitor which is a selective PIM-1 kinase inhibitor. It inhibits an enzyme in a signaling pathway that is very relevant to the biology of the disease. It has nice data so far that shows a reduction in symptoms, particularly spleen size and cytokines, as a single agent in patients who’ve already been on a JAK inhibitor.

Your MPN, Your Journey - How New Discoveries Will Impact Personalized Care

Other drugs may try to turn on mechanisms that have been turned off, like navtemadlin and selinexor. These drugs are focused on different pathways but with one unifying theme, which is the p53 pathway. It’s the master regulator of cell fate. In a normal situation, your cells would get cues to commit suicide if they were infected or corrupted in some way and that is governed by the p53 pathway, an intrinsic pathway that limits the cell’s life. The problem is malignant cells have co-opted that system and turned it off. They turn it off in different ways. Navtemadlin and selinexor, through having different mechanisms, act on trying to turn that pathway on and encourage that cell to die.

You’ll see drugs that get into the cell that affect pathways, drugs that get into the cell that try to turn on pathways, and drugs that try to use the immune system in different ways to go after the abnormal cell.

Dr. John Mascarenhas

Then you might see a drug like a calreticulin antibody, which inevitably will get a name. You’ll notice early on that it’s just letters and numbers and as the development goes on, it becomes funny names that don’t make any sense and then ultimately, when it gets to the commercial space, it will be a catchy name that could be marketed. The mutant CALR antibody drug by Incyte is a perfect example of what will be a “mab,” a monoclonal antibody, which is targeted at the CALR mutant protein expressed aberrantly on the surface of the cell and is a marker for those abnormal cells. What better way to attack an abnormal cell than to have a selective marker? It’s like a handshake. It’s not even a drug; it’s a peptide. It’s a protein that binds that and by doing that, internalizes that protein complex, and that leads to the death of that cell selectively.

Your MPN, Your Journey - How New Discoveries Will Impact Personalized Care

Approaches like that will be very fascinating. Those are immune-based approaches. They have BiTEs (bispecific T-cell engagers) that multiple companies are developing, which introduce T cells in a myelofibrosis patient to the abnormal cell by having two ends of that antibody — one that goes after the CALR, for example, and the other one that goes after CD3 on a T cell — and introduces the two cells together so that that T cell does what it should have done in the first place: recognize and create a response to that abnormal cell.

You’ll see drugs that get into the cell that affect pathways, drugs that get into the cell that try to turn on pathways, and drugs that try to use the immune system in different ways to go after the abnormal cell. These are the general themes.

Your MPN, Your Journey - How New Discoveries Will Impact Personalized Care

Considering a Clinical Trial

Andrew: Some drugs are being studied at different levels. What would you say about considering enrolling a patient in a trial once there’s a clear picture of their case? Is there one of these that could line up with that? Take us through the thinking and discussion between a doctor and a patient about considering being in a trial.

Dr. Mascarenhas: I have to acknowledge that being on a trial is scary. I hear this all the time: guinea pig. You feel as though you may be experimented on. I always try to caution patients from that mentality because if you have a disease like myelofibrosis that is frightening to have in itself and can limit the quality of life and maybe even the time that you have, then it warrants consideration to do better than the MPN treatment standard of care. The standard of care, which is JAK inhibitors, has benefits for sure, but it’s incomplete for many patients.

Your MPN, Your Journey - How New Discoveries Will Impact Personalized Care

The consideration for trials hinges on the patient’s goals and desires. Clinical trials may not be reasonable for every patient. Geography influences clinical trials. If you live in a rural area, the distance to a center offering a clinical trial may preclude you from participating. We know other factors may also get in the way of joining clinical trials, like language barriers, cultural barriers, and financial barriers.

I would encourage any patient who sees a specialist and goes to a tertiary care center to at least seek a consultation. This will help them understand what someone who does this full-time thinks about their disease, to clarify or classify their disease, and what clinical trial options exist.

Trials should make sense. You have to ask questions so that you understand what you’re getting involved in.

Dr. John Mascarenhas

I’ve been around long enough to know ruxolitinib as INCB18424 before it was Jakafi. The drug was used in the clinic and we prayed that it was going to make a big difference and it did. It wasn’t enough of a difference, but it made a big difference. I remember those brave patients who were the first patients to get on that study. They set the tone for the whole field and the development of other therapies because of what they put themselves into. Those patients needed the therapy, but what they did allowed us to prescribe the drug to a lot of patients. It has a profound impact way beyond that individual.

Your MPN, Your Journey - How New Discoveries Will Impact Personalized Care

The reality is patients go on a clinical trial for themselves and that is what it should be, but you end up helping the greater good at the same time. You have to feel comfortable with joining a clinical trial. You have to read the consent form. You have to ask questions. What does it involve? What are the potential toxicities? What would be the consequences of participating in a trial?

I feel very comfortable saying that in 2025, any trial I’m aware of that’s offered to patients is an informed trial. These are not trials where we’re taking a random agent off a shelf, throwing it over there, and hoping that it works. These are drugs and agents that are vetted, have a rationale, and go through many layers of pre-testing before they go into humans. You have to trust your physician because if your physician is working with you, then the trial that’s offered to you would hopefully make sense. Trials should make sense. You have to ask questions so that you understand what you’re getting involved in.

Your MPN, Your Journey - How New Discoveries Will Impact Personalized Care

Getting the Test Drug vs. a Placebo

Andrew: You mentioned that people ask if they’re going to be a guinea pig. They also ask if they’re going to get the “good stuff.” In other words, they want to know if they’re getting a sugar pill or a placebo. Could you talk about that concerning these trials for drugs that are investigational now?

Dr. Mascarenhas: If you’re in a phase 3 study that’s randomized, a computer randomizes you to arm A or arm B. Arm A may be the active clinical trial agent and arm B could be a placebo, but that has to be disclosed in a consent form. That’s essential. You can ask the physician, “Do I get the study drug or is it going to be randomized? Is it going to be a placebo?”

But a placebo is not always bad. For example, in the MANIFEST-2 study or what’s currently enrolling in the SENTRY study with selinexor, you get randomized as a JAK inhibitor-naive patient with myelofibrosis to either Jakafi plus a placebo, so you’re still getting active therapy, versus Jakafi plus selinexor.

It would be unethical to give nothing to someone who needs treatment.

Dr. John Mascarenhas

The idea is: can we build upon the success of the standard of care? That becomes important. It would be unethical to give nothing to someone who needs treatment. It’s not unethical and it’s practical to give someone who needs treatment the standard of care plus a sugar pill, which is blinded, versus the standard of care plus the study drug to ask which treatment regimen is better.

You can ask your physician, but you’ll notice that most trials will allow crossover and that becomes important. If you get the placebo, which only the computer knows, at some interval, most trials will allow you to cross over to the active compound. It becomes a question of: do I get the active combination upfront or is it delayed? That’s a nuance that I want to stress. If you’re participating in a phase 1 or phase 2 study, you’re going to get the drug. Those are not placebo-controlled studies. You should always be getting the drug in those settings.

Your MPN, Your Journey - How New Discoveries Will Impact Personalized Care

What If I Have Other Chronic Conditions?

Andrew: Some of us have other conditions, like diabetes, high blood pressure, or a heart condition — for me, it’s chronic lymphocytic leukemia, which is fortunately pretty well-controlled— but we’re often excluded from trials depending on the condition. We understand the worry of the investigators. Is our data clean? Can you extrapolate from that? Can you talk about exclusion criteria and compassionate use?

Dr. Mascarenhas: The reality is there are biases in the way we do trials. We avoid patients who may be inappropriate and these are real patients who might be in need, but the trial may not be appropriate. These can be patients who have very significant kidney or heart dysfunction or a competing malignancy. Interestingly, CLL, which is more frequently seen in patients with MPNs, has different stages. Sometimes a study will allow patients who have a very indolent type of CLL to go on the study. But often, trials will be very particular, especially registration studies where they’re going for approval.

Your MPN, Your Journey - How New Discoveries Will Impact Personalized Care

The last thing a study needs is to have confounding data where they’re unclear whether they’re making something unrelated to the myelofibrosis worse or that condition is making the assessment of the drug harder to appreciate. There is a tendency to exclude patients who have extremes of comorbidities so not all comorbidities. If you have grade 1 heart failure, that’s often allowed in a study because that’s a reality of life.

There is a very strict inclusion and exclusion criteria, what we call eligibility criteria, which determine the ability to put someone on a study. Most of those are there for safety reasons to avoid causing additional problems with a drug because it’s not intended for that reason. Another reason why they’re there is if you have a very messy, patient population with lots of diversity and heterogeneity in organ function, etc., it can be very difficult to assess whether the treatment we’re giving is safe or effective. To some extent, out of necessity, we create some homogeneity out of the heterogeneity.

Compassionate use… requires a lot of regulatory oversight, approval, and effort, which is not provided by a company or anyone.

Dr. John Mascarenhas

Andrew: How about compassionate use? If somebody would otherwise be excluded, could their doctor make a plea for a late-stage patient?

Dr. Mascarenhas: Compassionate use is often not that compassionate. It’s trying to get access to a drug under an investigational new drug (IND) and creating a protocol for one individual. What is not always appreciated is while that sounds great, many steps go into that and it requires a lot of regulatory oversight, approval, and effort, which is not provided by a company or anyone. It’s the physician and whatever team members he can assemble to try to do that.

Your MPN, Your Journey - How New Discoveries Will Impact Personalized Care

Although compassionate use is an opportunity to get a drug, it’s often an opportunity plagued by the realities of a very cumbersome bureaucratic system that doesn’t make it very easy and timely to get to that drug. Although it’s there and in some cases helpful, it’s not always practical or realistic for people to get compassionate use and sometimes the access to those drugs is restricted by the FDA and/or the sponsor.

But compassionate use can sometimes be an opportunity to get a drug that wouldn’t otherwise be eligible and that’s key. If there’s a trial that allows the patient to get access, they often will not provide compassionate use because it would be felt unethical to allow someone to get access to a drug while all other patients would have to go through the normal routine of the clinical trial. This has to fit very strict criteria and is not always achievable.

Your MPN, Your Journey - How New Discoveries Will Impact Personalized Care

The Future of Treatments for MPN Patients

Andrew: We have ASH in the rearview mirror. You have other conferences during the year and you’re speaking at a number of them. You’re actively involved in research and seeing patients as well. I want to get where your head’s at as far as promise in the field, how you feel about it, and what people can do about it.

Dr. Mascarenhas: We are way further ahead than we were in 2005, 2010, and 2015. I’ve watched the field grow in terms of our understanding, the amount of attention and support that’s provided to this rather small area of hematology from the federal government in terms of NIH grants — in which we indulge in getting to try to help move the field forward independent of pharmaceutical interests — but as well as pharmaceutical interest and philanthropy. They all help grease this machinery of translational research and understanding. We have cadres of smart, well-intentioned PhDs, MDs, and MD-PhDs that are helping us understand the biology and that is directly translating into the clinic to help us fine-tune our treatment.

We’re trying to understand how to get access to and develop multiple therapies that could be used in different subsets of patients or different combinations.

Dr. John Mascarenhas

You look at ASH or EHA and see endless abstracts of agents that we didn’t even know about or targets that we didn’t even understand 10 years ago. I have to believe that’s going to translate ultimately to better therapies and multiple therapies. I don’t think it’s going to be one therapy fits all. We’re trying to understand how to get access to and develop multiple therapies that could be used in different subsets of patients or different combinations and that is something that I do feel optimistic about. I would say we’re moving forward in 2025 and beyond in rational combinations and allowing science to drive the advancements.

You’ve known me for a long time. I always feel positive. I walk to work and I’m enthusiastic every day I come in because I believe in the mission. We’re making strides. I see it in the patients that I treat, but I believe it for the future.

What Patients Can Do to Alleviate Symptom Burden

Andrew: For a patient who has significant anemia, declining platelet counts, an enlarged spleen, or whatever symptom they’re experiencing, what can they do that could make a difference in the short term?

Dr. Mascarenhas: If you’re having symptom burden, particularly if it’s interfering with your quality of life and activities of daily living, you should see a physician who specializes in hematology and, ideally, someone who has expertise in this area.

The longer one delays starting therapy, the less likely that therapy will be effective and that the effects of that therapy will be durable.

Dr. John Mascarenhas

A JAK inhibitor is the front-line therapy to try to address those aspects. It doesn’t preclude one from looking at clinical trials that might even be combinations upfront of a JAK inhibitor plus an active agent to see if one can get even better, deeper, and earlier responses. But at the very least, a JAK inhibitor to try to address symptoms because you don’t get extra points for suffering through symptoms. It’s harder to rescue if one delays treatment. The data is very clear about that. The longer one delays starting therapy, the less likely that therapy will be effective and that the effects of that therapy will be durable.

Andrew: You may live at a distance from one of the major centers where there is an MPN specialist, but there are MPN specialists. You refer to cadres of researchers and physicians who are working in this area and it makes sense to have a consultation with somebody like Dr. Mascarenhas at Mount Sinai or my doctor, Dr. Jamieson at UC San Diego. Fortunately, many others are studying this and working on it and understand these nuances, so you get personalized care for where you are now and where you may be headed.

Your MPN, Your Journey - How New Discoveries Will Impact Personalized Care

Final Takeaways on MPN Treatments

Andrew: This has been a helpful discussion. Is there anything you wanted to add, John, that we didn’t cover?

Dr. Mascarenhas: We covered all the major points and I conveyed my continued optimism. One boon that we have is it’s a very collaborative field. When you look at the abstracts, trials, and studies, you will see all the names that are listed, which reflects our collaborative nature. These are rare diseases. You can’t work in a silo. We’re all friends and colleagues. We all have a unified mission. We’re focused on that as an international team and that’s why I remain enthusiastic that we’re going to make the progress.

Andrew: Thank you for your collaboration and people. I’m seeing a lot of younger physicians and scientists interested in this area, so that gives us a great deal of hope. Dr. Mascarenhas, thank you for your devotion to us. We appreciate your time. We’re all bonded in this together. Remember: knowledge can be the best medicine of all.

Your MPN, Your Journey - How New Discoveries Will Impact Personalized Care

Conclusion

Tiffany: That discussion [ on MPN treatments ] was the definition of news you can use. Thank you, Dr. Mascarenhas and our patient advocate and moderator Andrew, for taking the time out of your busy schedules to keep The Patient Story community informed. If you are a patient, caregiver, partner, or advocate, consider being a voice leader in your community or with us at The Patient Story.

To be empowered is to be inspired. We want you to make informed decisions about your care and that includes being educated about the latest treatment options. Thank you again to our sponsors, Sobi and Incyte, for their support of our independent patient program and to all of our promotional partners. Until next time, I’m Tiffany Drummond, signing off and, on behalf of The Patient Story, thank you for watching.

Your MPN, Your Journey: How New Discoveries Will Impact Personalized Care
Hosted by The Patient Story Team
Dr. John Mascarenhas (Mount Sinai) and patient advocate Andrew Schorr share the latest breakthroughs in MPN care. Explore personalized treatments, cutting-edge therapies, and groundbreaking research that’s changing how MPNs are treated. Learn how new discoveries can improve your treatment options, help manage side effects, and enhance your quality of life.
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Incyte

Special thanks again to Sobi and Incyte for supporting our independent patient education content. The Patient Story retains full editorial control.


MPN Patient Stories

Andrea S. feature profile

Andrea’s Myelofibrosis & Essential Thrombocythemia Story

Andrea S., essential thrombocythemia (ET) progressing to Myelofibrosis Symptoms: Fatigue, anemia Treatments: Targeted therapy (JAK inhibitor)...

Holly’s Myelofibrosis Story

Holly S., Myelofibrosis Symptoms: Severe fatigue, throbbing pain in left calf, significant weight loss, itching and...
Ben H.

Ben’s Myelofibrosis with CALR Mutation Story

Ben H., Myelofibrosis Symptoms: None; caught at a routine blood testTreatments: Hydroxyurea & aspirin, ruxolitinib...
Doug A. feature profile

Doug’s Myelofibrosis Story

Doug A., Myelofibrosis Symptom: FatigueTreatments: ruxolitinib, selinexor (clinical trial)...
Kristin D.

Kristin’s Myelofibrosis Story

Kristin D., Myelofibrosis Symptoms: None; caught at routine blood workTreatment: Stem cell transplant...
Joseph C. feature profile

Joseph’s Myelofibrosis Story

Joseph C., Myelofibrosis Symptoms: None; caught at routine blood workTreatment: Clinical trial: VONJO (pacritinib)...

Categories
bendamustine (Bendeka) Bexxar CAR T-Cell Therapy Chemotherapy Follicular Lymphoma Gazyva Immunotherapy Metastatic Non-Hodgkin Lymphoma Patient Stories R-CHOP Treatments Vorinostat Zydelig (idelalisib)

Laurie’s Stage 4 Follicular Non-Hodgkin Lymphoma Story

Laurie’s Stage 4 Follicular Non-Hodgkin Lymphoma Story

Laurie, a Los Angeles resident, was diagnosed with stage 4 follicular non-Hodgkin lymphoma in 2006, when she was 46. Her journey to diagnosis began years earlier with vague symptoms—frequent sinus infections, a tendency for her right eye to dry out, fatigue, and a lump in her abdomen. Multiple doctors dismissed her concerns, with one attributing the lump to a hernia. But a diagnostician ordered a CT scan, and it revealed a grapefruit-sized tumor and spots on her lungs.

Interviewed by: Nikki Murphy
Edited by: Chris Sanchez

After undergoing a series of tests, including biopsies, Laurie learned she had follicular non-Hodgkin lymphoma, a type of cancer affecting the lymphatic system. Her initial response to the cancer diagnosis was shock, followed by depression and uncertainty about how to explain the situation to her young son and husband.

Laurie’s treatment regimen started with chemotherapy and a monoclonal antibody, which successfully reduced the tumors after 6 rounds. However, her cancer relapsed, and she explored additional treatment options, including a clinical trial using an HDAC inhibitor (therapy that helps control how cancer cells grow and divide by affecting the cancer cell DNA). It initially stabilized the cancer but ultimately failed after 11 months. Consequently, Laurie turned to alternative therapies, including radioimmunotherapy (delivering high dose radiation directly to the tumor cells) and a more aggressive chemotherapy regimen, but these also proved unsuccessful.

In 2011, Laurie enrolled in a clinical trial for a Pi3 kinase inhibitor (a treatment that works to block a pathway cancer cells use to grow and survive that can slow a cancer’s growth and help keep it under control), which kept her cancer stable for over 5 years, albeit not fully eliminating it. During this time, she learned about CAR T-cell therapy, a cutting-edge treatment using a patient’s own T cells to target cancer cells. While initially not available for follicular lymphoma, CAR T-cell therapy became an option for Laurie in 2018. She consequently underwent the procedure — a remarkable 7th line of cancer treatment. As a result, she achieved remission for the first time in 12 years. As of 2024, Laurie has remained cancer-free. Her oncologist considers her cured, as her CAR T-cells continue to be detectable in her system.

Throughout her treatment journey, Laurie faced numerous challenges, including the side effects of chemotherapy, radiation, and steroids. She developed avascular necrosis, which required hip surgery, a consequence of long-term steroid use. However, despite these struggles, Laurie’s battle with cancer transformed her into a passionate patient advocate. She now works with 3 nonprofits, helping others navigate cancer treatment and advocating for more accessible and less potentially toxic therapies like CAR T-cell therapy. Laurie emphasizes the importance of finding a specialized oncologist, self-advocacy, and the value of second opinions and clinical trials in managing cancer.

Laurie’s story underscores the evolving landscape of cancer treatment, particularly in the context of immunotherapy. She highlights the importance of staying informed and advocating for oneself or having someone advocate on their behalf, especially as new therapies emerge. Through persistence, resilience, and research, Laurie continues to support others facing similar battles. She shares her journey to inspire hope and grow awareness.


  • Name:
    • Laurie A.
  • Age at Diagnosis:
    • 46
  • Diagnosis:
    • Follicular lymphoma
  • Staging:
    • Stage 4
  • Symptoms:
    • Frequent sinus infections
    • Dry right eye
    • Fatigue
    • Lump in abdomen
  • Treatments:
    • Chemotherapy
    • Targeted therapy
    • Radioimmunotherapy

This interview has been edited for clarity. This is not medical advice. Please consult with your healthcare provider to make treatment decisions.


Thank you for sharing your story, Laurie!

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Related Cancer Stories

More Follicular Lymphoma Stories

Hayley H., Follicular Lymphoma, Stage 3B



Symptoms: Intermittent feeling of pressure above clavicle, appearance of lumps on the neck, mild wheeze when breathing and seated in a certain position
Treatments: Surgery, chemotherapy

Courtney L., Follicular Lymphoma, Stage 3B



Symptoms: Intermittent back pain, sinus issues, hearing loss, swollen lymph node in neck, difficulty breathing
Treatment: Chemotherapy

John S., Follicular Lymphoma, Stage 4



Symptom: Swollen lymph nodes

Treatments: Clinical trial, chemotherapy

Laurie A., Follicular Non-Hodgkin Lymphoma, Stage 4



Symptoms: Frequent sinus infections, dry right eye, fatigue, lump in abdomen

Treatments: Chemotherapy, targeted therapy, radioimmunotherapy
David shares his stage 4 follicular lymphoma diagnosis
David K., Follicular Lymphoma, Stage 4 Symptoms: Sharp abdominal pains, frequently sick, less stamina Treatments: Chemotherapy, immunotherapy, radiation, clinical trial, autologous stem cell transplant

Categories
Continuing the Dream Diversity, Equity, & Inclusion Medical Experts Patient Events

Overcoming Racial Barriers in Clinical Trials from a Lung Cancer Oncologist

Overcoming Racial Barriers in Clinical Trials from a Lung Cancer Oncologist

Marjory Charlot, MD, MPH, MSc, is a medical oncologist and health services researcher at UNC Lineberger Comprehensive Cancer Center. She primarily specializes in people who have lung cancer. Her research focuses on increasing awareness and access to clinical trials among Black communities and communities with low-income or persistent poverty.

Interviewed by: Nikki Murphy
Edited by: Katrina Villareal


Abbvie has helped sponsor this discussion by The Patient Story
Genmab
Karyopharm

Thank you to AbbVie, Genmab, and Karyopharm 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. This is not medical advice. Please consult with your healthcare provider to make treatment decisions.



Introduction

Nikki Murphy: Tell us about yourself.

Dr. Marjory Charlot: I’m a medical oncologist and health services researcher. I work at UNC Lineberger Comprehensive Cancer Center and primarily specialize in lung cancer patients. Part of my work is working in the hospital for patients who either have a suspicion of cancer or have a cancer diagnosis but are hospitalized for symptoms of their cancer or side effects from their treatment. As a health services researcher, my research focuses on increasing awareness and access to clinical trials among Black communities and communities with low-income or persistent poverty.

Outside of medicine, I’m a wife and a mom. I have two children, one in elementary school and one in middle school. I recently completed an aquathlon, a swim-run competition, which is a big deal for me because I don’t have a great relationship with swimming. I learned to swim as an adult, so it was a big accomplishment for me to be able to complete this duathlon, so that was exciting. I also love to travel and visit different places across the US or abroad. I also love to eat. I love various types of foods.

Dr. Marjory Charlot

When I completed my medical training, I knew that I wanted to be an oncologist. There was no question about that.

Dr. Marjory Charlot

A Winding Path to Medicine

Nikki: What was your number one driver to becoming a doctor?

Dr. Charlot: I knew from a young age that I wanted to become a doctor. I grew up in Mattapan, a neighborhood in Boston, and I was privileged enough to have a Haitian pediatrician who had his practice in the community and did house visits. The Haitian community where I grew up was tight-knit and it was informative for me to be able to see someone who shared my heritage be a physician and be one with the community, so I wanted to be exactly like him.

My path to becoming a doctor was not straight and narrow. After I graduated from college, I spent a couple of years working in different types of advocacy work related to education and moved on to teaching middle school students about health professional careers. After that, I got my degree in public health and then after that, I went to medical school. It was a winding path to medicine, but I knew that’s where I would end up eventually.

Why Oncology Became Her Calling

Nikki: How did you end up specializing in lung cancer?

Dr. Charlot: When I completed my medical training, I knew that I wanted to be an oncologist. There was no question about that. I felt like it was the field where you develop close-knit relationships with your patients, so that was a no-brainer. Oncology was the way that I wanted to go.

Concerning lung cancer, I was influenced by my mentor. When I started my training, there weren’t that many options for lung cancer. There was chemotherapy and that was pretty much it. However, during my training, there were a lot of new therapies coming up, like immunotherapy and targeted therapy. The excitement in the field drew me to want to be a part of this growing field concerning options for our patients. The field was getting to a place where we had more options to offer our patients other than chemotherapy itself and that’s where my love and compassion towards lung cancer grew.

Dr. Marjory Charlot

It was ingrained in me that we needed to think about the community and the circumstances that people are born in or the conditions they live in for the healthcare system to work.

Dr. Marjory Charlot

Growing Up in Mattapan

Nikki: What motivated you to go above and beyond and focus on helping an entire community get better access to health care and treatment options, including clinical trials?

Dr. Charlot: Mattapan is a predominantly Black community and interestingly enough, my street and pretty much my whole block were folks that immigrated to Boston. I have a Haitian background, so my interest in terms of thinking about communities draws from that experience.

I lived in two different worlds. I had the world where I grew up in Mattapan, but I also always went to Catholic school, which was outside of our neighborhood. I saw the dichotomy between the school in terms of the affluence of the area and some of the students who attended that school and my neighborhood where we’re very rich in culture and pride, and hardworking, but we didn’t have the same resources.

When I became a doctor, I did all of my training at a safety net hospital, so we cared primarily for people who were underinsured or had no insurance. It was the hospital where I was born, so it was ingrained in me that we needed to think about the community and the circumstances that people are born in or the conditions they live in for the healthcare system to work.

That’s where my whole approach comes from in terms of thinking about Black communities and the importance of ensuring that they have the knowledge and the awareness of all the resources available to ensure that they have access to care and can improve their outcomes through those connections. As a physician, I think about the Black community and understand ways how we need to make those connections together for us to thrive, do better, and live healthy lives.

Dr. Marjory Charlot

I used my background concerning patient and community engagement to improve access to clinical trials, cancer care, and high-quality cancer care.

Dr. Marjory Charlot

Developing the CREATE Initiative

Nikki: How did you end up at UNC?

Dr. Charlot: I was recruited to UNC primarily to work as a thoracic oncologist, so my specialty in lung cancer, as well as develop a program that was focused on clinical trials and increasing equity in clinical trials. As a result of my research and clinical background, I ended up starting the CREATE initiative, which is Cancer Research, Equity, and Advocacy Through Engagement. This initiative speaks to the strong community focus and the work that we do with our community partners for the healthcare system to work and for the treatments to get to the people that they were designed to treat. I used my background concerning patient and community engagement to improve access to clinical trials, cancer care, and high-quality cancer care.

Most Common Lung Cancer Symptoms

Nikki: We understand that there’s a wide range of symptoms, but what are the most common symptoms of lung cancer? And what should people never ignore?

Dr. Charlot: Screening in general is meant to detect cancers early, before they cause symptoms. But generally speaking, by the time a patient is diagnosed with cancer, medical oncologists see patients after the cancer has spread or advanced and not in a stage where it could be cured with surgery. However, things have changed with cancer where we’re using chemotherapy and immunotherapy even for earlier cancer stages.

Common symptoms are generally related to shortness of breath, coughing (particularly coughing up blood), and sometimes weight loss. Those are the top three that patients describe in terms of things that they’ve noticed when they’re diagnosed with cancer.

If the cancer has spread, they could present with various symptoms, like a headache if the cancer has spread to the brain or pain in various areas, like in the bones or the joints. There could be a wide range of symptoms depending on where the cancer is.

The most important thing is to be aware that cancer screening is an option, particularly for people who have had a long history of smoking. Twenty pack-years is the recommendation. Screening is for those who don’t have symptoms, but if they do have symptoms, it’s another reason to see their doctors so they can get examined and evaluated for potential cancer.

Dr. Marjory Charlot

It’s important to be able to test these drugs on a variety of people and understand how these treatments impact various groups.

Dr. Marjory Charlot

Demystifying Clinical Trials

Nikki: We know that trials aren’t for everyone. What would you say specifically to Black and African Americans to convince them to learn about clinical trials?

Dr. Charlot: Clinical trials are an opportunity to get access to new treatments that are not currently available. For the Black community in particular, we know that outcomes are worse when it comes to cancer survival and mortality rates. Clinical trials provide an opportunity to get access to new drugs, which ideally will prolong life.

It’s important for all patients, regardless of background, to have access. We don’t know how these drugs are going to affect people, whether it’s based on their environment, socioeconomic status, or race. It’s important to be able to test these drugs on a variety of people and understand how these treatments impact various groups.

A Patient’s Clinical Trial Success Story

Nikki: Can you think of a specific story that shows how impactful a trial can be for someone?

Dr. Charlot: I started the CREATE initiative at Lineberger and we’re in the process of completing a research grant that I have, which is building a mobile app for Black women with breast cancer to see if it can help increase discussions about clinical trials with their providers. One of our patient research partners shared her story about participating in a trial where the trial led to her being cancer-free for a very long time in that she’s been able to see this drug become a standard of care for breast cancer treatment.

It’s important to acknowledge the historical past and some of the mistreatment that Black communities and individuals often get within the medical care system.

Variety of chemotherapy drugs in bottles

This goes to show that when going into a trial, we don’t know whether or not these drugs are going to work. What we do know is that when you’re in a clinical trial, you’re under such close follow-up, which gives you even an extra layer of eyes of people who are watching how you’re doing. If these drugs prove to be better than the standard of care, these drugs end up helping people live longer.

It’s fascinating and wonderful to be able to work with someone who’s been through this whole process of participating in a clinical trial and seeing that her participation led to the approval of a new drug that is now being used for breast cancer patients. There’s no better story than to live through the process of being in a clinical trial and to see how that participation led to the approval of a drug that more women and other people with breast cancer can benefit from.

Overcoming Barriers in Black Communities

Nikki: What would your message be to the Black and African-American community who are fearful of clinical trials?

Dr. Charlot: We know that our healthcare system and our research enterprise in this country have not been the best, particularly for our Black communities. At the same time, it’s important to acknowledge the historical past and some of the mistreatment that Black communities and individuals often get within the medical care system. Acknowledgment is at the forefront.

It’s also important to know that there are safeguards in place with clinical trials. It’s important for us, specifically as Black individuals, to be a part of clinical trials because it gives us opportunities that we would potentially not have to access newer drugs. Acknowledge the past and understand that we have a part and the right to have access to newer treatments and interventions.

patient with doctor

We need to understand where our patients are coming from, know what their needs are, and partner with them.

Dr. Marjory Charlot

The Role of Black Physicians in Healthcare

Nikki: What do you think healthcare professionals can do better when building trust with the Black and African American community?

Dr. Charlot: As a Black physician and even for healthcare providers who are not Black, we need to be one with our community. We need to understand where our patients are coming from, know what their needs are, and partner with them. If we do these separately in our silos, it doesn’t help improve access to care. It doesn’t help our communities thrive and live healthy lives. Making connections is what’s helped me in the work that I do and hopefully helping the patients that I’ve had the privilege to take care of over these past couple of decades as a physician.


Abbvie has helped sponsor this discussion by The Patient Story
Genmab
Karyopharm

Special thanks again to AbbVieGenmab, and Karyopharm for their support of our patient education program. The Patient Story retains full editorial control over all content.


Stories from Raleigh, NC

Dr. Colin Ottey

The Importance of Cancer Screening | Dr. Colin Ottey



An internal medicine physician discusses healthcare access, preventative care, patient trust, and how both doctors and patients can improve relationships for better outcomes.
Lemuel Eley feature profile

The Importance of Cancer Screening | Lemuel Eley



Heart attack survivor at 44 shares his story, advocating for health screenings and proactive care in the African-American community.
Dr. Marjory Charlot

Dr. Marjory Charlot, Oncology



UNC oncologist discusses increasing awareness and access to clinical trials among Black communities

Roshonda C., Rectal Cancer, Stage 4



Symptoms: Blood in stool, blood from rectum after intercourse, sensation of incomplete bowel movements
Treatments: Chemotherapy, surgery, radiation

Categories
Alimta (pemetrexed) Carboplatin Chemotherapy Clinical Trials Immunotherapy Keytruda (pembrolizumab) Lung Cancer Non-Small Cell Lung Cancer Patient Stories Radiation Therapy Treatments

Natalie’s Stage 4 Non-Small Cell Lung Cancer Story

Natalie’s Stage 4 Non-Small Cell Lung Cancer Story

Interviewed by: Nikki Murphy
Edited by: Chris Sanchez

Natalie, who hails from Atlanta, GA, was diagnosed with stage 4 non-small cell lung cancer in June 2020. Her diagnosis followed a challenging 6-month period of inconclusive tests and misdiagnoses due to her age and non-smoking status. Her doctors initially attributed her symptoms, primarily fatigue and a persistent cough, to less serious conditions such as allergies or asthma. Despite undergoing multiple diagnostic procedures, including x-rays, CT scans, biopsies, and PET scans, Natalie only received her cancer diagnosis after one of her lungs collapsed during a biopsy.

Natalie was overwhelmed by the stage 4 diagnosis, associating the prognosis with a death sentence. Her cancer had already spread to both lungs and her lymph nodes, and her oncologist confirmed that there was no definitive cure. Natalie immediately began chemotherapy and immunotherapy treatments. While she managed the physical side effects, particularly severe fatigue, she continued working throughout her treatment, with few people aware of her diagnosis.

Over the course of 4 years, Natalie underwent 2 clinical trials after her cancer progressed, neither of which were successful. The first trial, at Emory Hospital, left her feeling worse than she did on chemotherapy and required multiple hospital visits. The second trial, in Nashville, produced no significant side effects. After these trials failed, she returned to chemotherapy, which has stabilized her cancer’s growth for now.

Beyond the physical challenges, Natalie has also struggled with the mental toll of her stage 4 non-small cell lung cancer. Therapy, her husband’s unwavering support, and her close-knit group of friends and family have been essential to her well-being. She acknowledges that at times she considered giving up treatment due to exhaustion but found renewed determination through the support of her loved ones and her desire to live and experience more of life.

Recently, Natalie’s pulmonologist informed her that she might be a candidate for a double lung transplant, a procedure that could potentially offer her a cure. She is in the early stages of the process and hopes that her cancer remains confined to her lungs so she can be placed on the donor list.

Natalie emphasizes the importance of advocating for lung cancer awareness, noting that anyone with lungs is at risk, not just smokers. She encourages others facing similar challenges to try to keep going, acknowledging the mental and physical difficulties of battling cancer. Her message is one of resilience and the importance of not giving up, even when the path is painful and difficult.


  • Name:
    • Natalie B.
  • Age at Diagnosis:
    • 33
  • Diagnosis:
    • Non-small cell lung cancer
  • Staging:
    • Stage 4
  • Symptoms:
    • Persistent cough
    • Fatigue
  • Treatments:
    • Chemotherapy
    • Immunotherapy
    • Clinical trials
    • Radiation (palliative)

This interview has been edited for clarity. This is not medical advice. Please consult with your healthcare provider to make treatment decisions.


Thank you for sharing your story, Natalie!

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Lisa G., Non-Small Cell, ROS1+, Stage 4 (Metastatic)



Symptoms: Persistent cough (months), coughing up a little blood, high fever, night sweats
Treatments: Chemotherapy (4 cycles), maintenance chemo (4 cycles)
...

Tara S., Non-Small Cell Lung Cancer, ALK+, Stage 4 (Metastatic)



Symptom: Numbness in face, left arm and leg

Treatments: Targeted radiation, targeted therapy
...
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Luna O.

Luna O., Non-Small Cell Lung Cancer, ROS1+, Stage 4 (Metastatic)



Symptom: None involving the lungs; severe abdominal pain

Treatments: Chemotherapy, targeted therapy

Donnita B., Non-Small Cell Lung Cancer, Stage 1A



Symptom: None

Treatment: Surgery

Jeff S., Non-Small Cell Lung Cancer with EGFR exon 19 Deletion, Stage 4



Symptom: Slight cough

Treatments: Surgery, radiation, chemotherapy, targeted therapy
Eugenia H. feature profile

Eugenia H., Poorly Differentiated Non-Small Cell Lung Cancer, Stage 4



Symptoms: Chest tightness, wheezing, weight loss, persistent high pulse rate, coughing up blood, severe bleeding from the mouth

Treatments: Chemotherapy, radiation therapy (external beam radiation therapy, brachytherapy & CyberKnife), cryotherapy, surgeries (tracheostomy & emergency bowel obstruction surgery), immunotherapy

Stephanie W. feature profile

Stephanie W., Non-Small Cell Lung Cancer, ALK+, Stage 2B



Symptoms: Persistent cough, wheezing
Treatments: Surgery (bilobectomy), chemotherapy, targeted therapy
Categories
Bispecific Antibodies Chemotherapy EGFR Lung Cancer Patient Stories Radiation Therapy Stereotactic body radiotherapy (SBRT) Surgery Treatments

Filipe’s Stage 4 Lung Cancer with EGFR exon 19 Deletion Story

Filipe’s Stage 4 Lung Cancer with EGFR exon 19 Deletion Story

Interviewed by: Taylor Scheib
Edited by: Katrina Villareal

Filipe P. feature profile

Filipe was diagnosed with stage 4 lung cancer at 36. He reflects on the challenges and critical decisions that shaped his treatment path. Being a nonsmoker, he was shocked by his diagnosis following a severe headache that prompted a brain MRI, revealing multiple metastases in the brain and a primary tumor in the lung. Despite disbelief and seeking second opinions, doctors confirmed the advanced stage of his condition.

The treatment began with brain surgery to address a 4 cm metastasis. Biomarker testing revealed an EGFR mutation, enabling targeted therapy that initially worked well. However, disease progression after nine months necessitated further interventions, including chemoablation for kidney metastases and SBRT for lung activity. Eventually, a new line of treatment with a bispecific antibody offered hope when options dwindled.

Managing side effects became a significant focus, especially as the current treatment led to severe skin issues and nail problems. Adjusting the treatment schedule provided some relief. Emphasizing the importance of second opinions and advocating for personalized care, Filipe highlights the need for patients to be informed and assertive. Despite setbacks and fears of running out of options, he remains hopeful, crediting research and innovation in lung cancer treatments for extending his life.


  • Name: Filipe P.
  • Age at Diagnosis:
    • 36
  • Diagnosis:
    • Lung Cancer (NSCLC)
  • Staging:
    • Stage 4
  • Mutation:
    • EGFR exon 19 Deletion
  • Symptom:
    • Headache
  • Treatments:
    • Surgery: to remove brain metastasis
    • cryoablation: to remove kidney metastasis
    • Targeted therapy
    • SBRT
    • Bispecific antibody
Filipe P.

Johnson & Johnson - J&J

Thank you to Johnson & Johnson for supporting 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 to make treatment decisions.



Introduction

I was diagnosed with stage 4 lung cancer at the age of 36. I’m married and I have a daughter. I have electronic hobbies.

Before my diagnosis, life was well. I was an IT systems administrator for an insurance company. My daughter was five years old when I was diagnosed.

The MRI revealed seven brain metastases and a 4 cm metastasis on the back of my head.

How I Found Out I Had Lung Cancer

I used to say I’m healthy all the time. I don’t have behaviors that justify my diagnosis, so it was a shock.

I was very lucky because my diagnostics took one day. When I had a headache, I went to the doctor and the first thing the doctor asked me to do was a brain MRI. When I was in the MRI machine, the technician asked me to wait because he wanted to call the doctor. I asked him why because the result takes at least one week. He said the doctor needed to see it.

The MRI revealed seven brain metastases and a 4 cm metastasis on the back of my head. For the doctors, it was very easy to diagnose because there was evidence. I had brain surgery two weeks after my MRI. They told me that the primary cancer would probably be lung because lung cancer usually metastasizes to the brain very quickly. They did a CT scan and biopsied the primary site and confirmed that I had stage 4 lung cancer.

At the appointment with the doctor, my wife was with me. When he said that it was cancer, I didn’t want to believe it because I never smoked in my life. I was healthy. I usually don’t go to the doctor, so it was very awkward for me. I started thinking about second opinions, but the doctor said there was no doubt about it. It was a shock.

Filipe P.
Filipe P.

Preparing for Brain Surgery

I went to the hospital. They double-checked everything with a CT scan and confirmed that it was lung cancer.

The first CT scan showed lesions on my liver. Fortunately, it was benign, but they found cancer in my bones, my left lung, and my head. They told me that I needed brain surgery right away because the 4 cm metastasis on my brain wouldn’t go away with other therapies. The brain is the last place a patient wants to have surgery.

The doctor said it was a very easy surgery. When they removed the bone, they were able to immediately take it out.

I started at a private hospital where I was diagnosed. They wanted me to undergo radiotherapy for my brain. I asked for a second opinion at a cancer center and they said the brain metastasis would not respond to radiotherapy and that I needed to have brain surgery. Because I’m a nonsmoker patient, I will probably have a mutation and if I’m eligible to undergo targeted therapy, usually the metastases respond very well to this kind of therapy.

I started to be treated at the cancer center. I had brain surgery to remove the biggest metastasis. After it was confirmed that I had the EGFR mutation, I started with a targeted therapy that’s very common for EGFR patients.

Second opinions are very important. There is a small margin of error in this disease. If you don’t choose the treatment well, you may not be able to choose another treatment. Listening to the doctors is very important. Get a second opinion or even a third opinion.

There were no other options for me at the time. I was very lucky because the metastasis was on the surface, so the doctors didn’t need to navigate into my brain to remove it. It only took 50 minutes. The doctor said it was a very easy surgery. When they removed the bone, they were able to immediately take it out. They didn’t need to do a whole lot.

Brain surgery is tough to think about, but it needs to be done. I wrote a letter saying goodbye to my family for them to open in case I die. Fortunately, everything went well and 24 hours later, I was standing up and walking.

Filipe P.
Filipe P.

Learning About Biomarkers

At the time, I didn’t understand why biomarkers were so important. Knowing your biomarker will define what kind of treatment you can have. It’s an expensive exam, but it’s very much needed because the biomarker will allow you to choose the best treatment for your cancer. The biomarker could save your life.

Targeted Therapy Worked for Nine Months

The average progression-free survival of the targeted therapy that I underwent is 18 months. I had a very short run. It only worked for nine months. The first few months were very good because it cleared four brain metastases. It also cleared my bone and reduced the cancer in my primary site.

After three months, I started to have early progression. A metastasis appeared in my kidney. We did a needle biopsy and a biomarker test to confirm if it was the same cancer because it’s very unusual for lung cancer to metastasize on the kidney. When it was confirmed that it was the same cancer, we did cryoablation on the kidney. We froze the metastasis with argon to kill the cancer cells. I also had SBRT on my lung because my lung started to have activity on the primary site based on a PET scan.

After nine months, in August 2023, I had severe progression. At the time, I had no other options on the market.

Knowing your biomarker will define what kind of treatment you can have.

Finding Another Line of Treatment

I was very lucky because my current treatment, which is a bispecific antibody, is only used for EGFR exon 20 and I am exon 19. I was very lucky because I had no options left. Amivantamab appeared and I had a great response to it.

I was very lucky because the drug came out. It’s frightening to think about running out of options and only relying on drugs that aren’t effective for your disease.

It’s similar to the sensation of when you receive the diagnosis thinking that you’re going to die, but this time, I have more information. I know exactly what my options are and even though they’re very few, I’m more aware of what’s happening. In the beginning, everything is new and you start to collect more information. But when I had the progression, I knew exactly what was going to happen.

Filipe P.
Filipe P.

Side Effects of the Current Line of Treatment

With targeted therapy, you can take one pill a day at home and have a normal life. With amivantamab and chemotherapy, you need to stay at the cancer center for six hours every three weeks. It’s not targeted, so it attacks the cancer cells but also the healthy cells, so you need to deal with the side effects.

It’s not as comfortable as targeted therapy. You need to reorganize your life according to the infusion days. If the toxicity is too high, I can postpone for one week, so sometimes I do four-week intervals instead of three. The major side effect is the skin and that’s why I have these pimples all over my body. I also have a lot of nail problems.

The side effects started to manifest weeks after taking the drug. It started with pimples and because I’m on blood thinners as well, everything was full of blood. After two or three months, I reached the peak of my side effects, and the side effects started to smoothen. Right now, only the nails are my major problem.

I used to have various scalp problems, pimples, and blood, but after almost 11 months, it’s only the nails and scalp. I control it with topical corticoids. I used to put a lot of cream, but it wasn’t enough. I need to take corticoids when I have treatments; otherwise, the skin becomes very red and has sunburn-like pain.

The rash is very tough because, for example, when I take a bath, I cannot use a towel and rub my skin. After all, it hurts a lot. I need to dry it very carefully with a towel. I stopped wearing white because you will see blood sometimes. The pain is also associated with that. Sometimes I’m unable to do normal things when I experience the peak of my side effects. For example, I cannot wear sneakers because it’s closed and I have nail problems on my feet, so I wear flip-flops all the time. The main problem is it doesn’t heal. Whatever you do, it doesn’t heal 100%. It can get better, but it never heals.

The toxicity starts to accumulate. In the beginning, it’s only one or two nails. Nowadays, it’s all of them. I only have one finger without problems. The rash is tough, but at some point, it starts to be manageable because you know your body, so you know what to do and know to avoid some troubles.

I’m a stage 4 lung cancer patient with brain metastasis. Forget the skin.

Communicating with My Doctors About the Side Effects

Doctors need to be careful with how to deal with their patients. They usually say that if they cannot control the side effects, treatment may be stopped and the patient starts to hide their side effects because they’re afraid of stopping treatment.

My dermatologist told me that in the beginning. If my skin becomes very bad, we need to stop treatment. I asked her, “What is the threshold?” I’m a stage 4 lung cancer patient with brain metastasis. Forget the skin. I started to understand when things go very bad with the rash and why we may need to stop treatment.

Treatment can be flexible. Instead of every three weeks, you can do it every four weeks, like I do now. One week can make a lot of difference for patients. A patient needs to know that everything is flexible.

I’m very happy with my current doctor, who’s my third doctor. You need to advocate for yourself. With all due respect, doctors need to understand that they are working for us and not the other way around. The patient has the power. He can stop treatment. He can postpone treatment. It’s our life, so we have a say and we need to be heard. Otherwise, we can change the doctors or change the medical team. Everything can change.

Filipe P.

The Fear of Running Out of Treatment Options

Running out of options is scary. Research is very important. Without research, people would run out of treatments. Treatment can save lives. I’m an example of that. I believe that if it wasn’t for the drug I’m currently on, I wouldn’t be here, so it’s very important to have options.

Cancer is a monster, but there is hope.

My Biggest Advice for Lung Cancer Patients

There has been more development in lung cancer in the last five years than in the last 50, so there are a lot of things happening. Don’t look at the statistics. The data online is outdated. There is a lot of hope. Cancer is a monster, but there is hope.


Johnson & Johnson - J&J

Special thanks again to Johnson & Johnson for its support of our independent patient education content. The Patient Story retains full editorial control.


Filipe P. feature profile
Thank you for sharing your story, Filipe!

Inspired by Filipe's story?

Share your story, too!


More EGFR Lung Cancer Stories


Jeff S., Non-Small Cell Lung Cancer with EGFR exon 19 Deletion, Stage 4



Symptom: Slight cough

Treatments: Surgery, radiation, chemotherapy, targeted therapy

Jill F., Non-Small Cell Lung Cancer with EGFR Exon 19 Deletion, Stage 1A



Symptom: Nodule found during periodic scan

Treatments: Surgery, targeted therapy, radiation
Filipe P. feature profile

Filipe P., Non-Small Cell, EGFR 19del, Stage 4 (Metastatic)



Symptom: Headache
Treatments: Surgery (to remove brain metastasis), cryoablation (to remove kidney metastasis), targeted therapy, SBRT, bispecific antibody
Leah P.

Leah P., Non-Small Cell, EGFR 19del, Stage 4



Symptoms: Persistent dry cough, shortness of breath, heaviness in the chest, coughing up blood, weight loss, right rib pain, right shoulder pain
Treatments: Targeted therapy, chemotherapy, radiation (SBRT)

Tiffany J., Non-Small Cell, EGFR+, Stage 4 (Metastatic)



Symptoms: Pain in right side, breathlessness
Treatment: Clinical trial (osimertinib & ramucirumab)

Categories
Chemotherapy HER2-Mutant Immunotherapy Lung Cancer Non-Small Cell Lung Cancer Patient Stories Treatments

Samantha’s Stage 4 HER2 Non-Small Cell Lung Cancer Story

Samantha’s Stage 4 HER2-Lung Cancer Story

Interviewed by: Stephanie Chuang
Edited by: Katrina Villareal

Samantha M. feature profile

At 37, Samantha was diagnosed with HER2 non-small cell lung cancer. Her symptoms started with a cough and chest pressure, so she went to urgent care. A cancer diagnosis was one thing, but a lung cancer diagnosis with no smoking history was mind-numbing to her. This is Samantha’s story of navigating a lung cancer diagnosis young and discovering a rare biomarker too.


  • Name: Samantha M.
  • Age at Diagnosis:
    • 37
  • Diagnosis:
    • Non-Small Cell Lung Cancer (NSCLC)
  • Staging:
    • Stage 4
  • Mutation:
    • HER2
  • Symptoms:
    • Persistent cough
    • Chest pressure
    • Fatigue
    • Weight loss
  • Treatments:
    • Chemotherapy
    • Immunotherapy
Samantha M.

Bayer

Thank you to Bayer 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.



I went on a women’s trip in March 2024. When I came back from the trip, I developed a cough and noticed some pressure on my chest.

Introduction

I was born in California, raised in Hong Kong and the UK, and went back to the US around 12 years ago. I’m an active, outdoor adventurer. I love hiking, backpacking, camping, and anything to do with nature and being outside.

My husband Justin and I have been married for seven years. He is my absolute world and soulmate. I also have a nine-year-old German Shepherd.

Samantha M.
Samantha M.

Pre-diagnosis

Initial Symptoms

I went on a women’s trip in March 2024. There were 20 of us going on this adventure together even though I had never met them before. We were going to travel to India for 10 days. Before the trip, everything felt completely normal.

When I came back from the trip, I developed a cough and noticed some pressure on my chest. The air is not the best in India. A lot of people developed a cough, so I didn’t think anything of it, but the chest pressure was bothering me.

Two weeks after my trip, I was still hiking 4 to 5 miles a day, but there was a lot of pressure going on. I went to urgent care where a doctor listened to my chest and said, “Let’s do a chest X-ray to see what’s going on.”

The results showed that my entire left lung was full of fluid and fully collapsed. He said, “You need to go to the emergency room immediately.” I was still very naive then, thinking it was something I contracted from my trip.

They said, ‘We had a chance to look at a biopsy of one of the lesions in your liver and the fluid in your lungs, and it’s looking to be more and more like cancer.’

Diagnosis

Getting a Cancer Diagnosis

I went to the emergency room and they admitted me right away. They put in a chest tube, which was not a pleasant experience, and ended up draining 3 liters of fluid from my lung. They took that off for testing and did multiple CT scans. Even though I was admitted to the hospital, I was getting information about my scans through the apps. My result came through before the doctor even spoke to me. It said multiple lesions on the liver and lungs.

The infectious disease doctor came in and started asking me a ton of questions. They thought I might have tuberculosis because I’d lived and traveled to a lot of foreign countries, so they were very confused and running tons of tests.

Unfortunately, on day three of the hospital admission, they said, “We had a chance to look at a biopsy of one of the lesions in your liver and the fluid in your lungs, and it’s looking to be more and more like cancer.” They couldn’t give me a guarantee at that point, but this was looking like it. They said, “We’re going to discharge you. We’ll wait for confirmation, but we’re lining up an oncology appointment for you right away.” That’s when my world spiraled.

Samantha M.
Samantha M.
Playing the Waiting Game

We were living in Missoula, Montana, where my husband was stationed. The wait for the general oncologist was two weeks. There was no specialist there. After all, it was such a small town. That period was awful. It was confirmed through the app that I did have cancer, but I had no doctor to bounce anything off or ask questions.

At that point, it didn’t say what stage I was, and not being too familiar, I didn’t know what stage 1 versus stage 4 meant. I had no idea. I didn’t know anything other than I had non-small cell lung cancer.

I was spiraling on Google, which is not your best friend at this time of diagnosis. I figured out I was stage 4 and learned the five-year survival rate. I was doing more digging and came across mutations all this information on mutations.

I was eventually diagnosed with HER2 mutation, which was one I had never heard of.

When I went into that initial oncology visit, I had a list of questions, but the number one was if I could get a biomarker test for genetic mutations. He said, “Absolutely. It was on my list. You’re good because I know a lot of oncologists in these smaller towns are still not aware of these biomarker testing and treat lung cancer when someone could have a targetable mutation.”

I learned a lot about mutations during that two-week waiting period. I was eventually diagnosed with HER2 mutation, which was one I had never heard of. I didn’t come across it on any websites. It was a two-week window of the unknown with the fear and concern that I didn’t have long to live.

At my first oncology appointment in Missoula, he told me that I was stage 4, I was terminal, and had nine months to live. He told me before he even knew what mutation I had. No one should be told how long they have to live like that. It doesn’t help anyone. It set my mind back a long way. It was devastating.

Samantha M.
Samantha M.
Reaction to the Diagnosis

My husband, who was a 19-year veteran at this point, used to be a combat medic in Iraq and Afghanistan, so he’s seen a lot and I had never seen him cry ever. When I got that diagnosis in Missoula, he went outside the hospital and broke down. That was hard to see and almost harder for me than receiving the news personally. We’re so young. It was heartbreaking because he’s my soulmate. Knowing that I’m not going to be around and be with him when we’re 80 years old is gut-wrenching.

It hit him hard. He’s been an incredible caregiver. He’s been to every single appointment. He now handles the app for me and looks at all of my results. He’s been exceptionally supportive. I couldn’t ask for a better caregiver, but I would say it’s probably had more of an impact on him than on me.

Honestly, I had a breakdown… I thought that was the end of my journey because there was no primary targeted treatment for HER2.

Seeing a Lung Cancer Specialist

My husband said, “We’ll see this oncologist here, but let’s get you to a research hospital. Let’s see if the army will move us.” Within a month, the army approved the move. We were 45 minutes away from the Huntsman Cancer Institute. They have been so supportive and my work has also been so supportive.

I’m very grateful because I know a lot of people are not in that situation, especially those who are young, have cancer, and work full-time jobs. We put our house up for sale and within a month of my diagnosis, we had fully moved to be settled and to see a lung oncologist in Salt Lake City.

I learned to advocate for myself constantly. I was pretty forceful in messaging the Huntsman saying, “I need to get in as soon as possible. The general oncologist referred me. This is their letter.”

Samantha M.
Samantha M.

I was fortunate to get the best thoracic oncologist at the Huntsman. They looked at my chart and saw the severity of my stage 4 diagnosis. They got me in very quickly and wanted to redo my scans. They did a CT scan and a PET scan, which I hadn’t had at that point. They said, “We’re sending biomarker testing off the blood and also take a sample from Missoula and submit that as a tissue sample.”

They didn’t want to start any treatment until my biomarker test results came back, which took about two weeks. Meanwhile, my lung was continuing to fill up with fluid, so I had to get drained regularly. I was still active and nothing was stopping me. I was hiking at 10,000-foot elevation and I had no issues, but I felt very, very tired.

My biomarker test results came back and said HER2. I had never heard of HER2 in my life. I thought, “What on earth is this? What am I going to do with this?”

Honestly, I had a breakdown because I had been part of groups that talked about EGFR and ALK, all these great drugs, and people doing so well as young people on these targeted therapies. I said, “This is it. I keep on getting hit over and over again with bad luck and this is the final straw.” I thought that was the end of my journey because there was no primary targeted treatment for HER2.

Learning About the HER2 Biomarker

I started researching on Google, which wasn’t the best idea because when you search lung cancer and HER2, it says you do not have a very good prognosis at all and that wasn’t what I wanted to hear. That and not seeing anything about a primary targeted therapy was heartbreaking.

Samantha M.
Samantha M.
Finding Hope While Learning from Other Patients’ Experiences

I was introduced to someone who is part of an exon 20 group. I spoke to her within 24 hours of knowing that I had HER2 and she spent about an hour explaining everything: what was on the horizon as far as treatment was concerned, what was currently under clinical trials, and all of this hope.

I went from absolute turmoil, thinking this was literally the end, and that I have the worst prognosis to there could actually be some hope here and that changed my entire attitude. A lot of HER2 patients, when they find out about their mutation, aren’t told about the hope. They aren’t told about what’s coming. People have no idea unless they’re educated by other people.

I wanted to start treatment, so we decided on traditional chemo and immunotherapy and started that within a week.

Treatment

Treatment Options for HER2 Mutation

My oncologist is incredible. He called me right away and said, “Look. This isn’t what I was expecting either, but this is what we have.” He was trying to find silver linings. He said, “You have to come in every three weeks to get treatment, but your mutation works with immunotherapy. Your mutation can work with traditional chemo.” He was giving me some hope and that’s all I needed to hear.

He wasn’t an expert in HER2. I don’t think he has any other HER2 patients, but I was also fortunate because my coworker’s husband’s best friend is a HER2 expert and he’s been an incredible resource who I can text and get information or reassurance. Having those two resources has been invaluable.

My oncologist laid out what chemotherapy and immunotherapy I would be on. He also offered up a clinical trial, which split chemo and immunotherapy separately by a week, instead of combining them for a couple of rounds. He thought that I would be a good candidate.

Samantha M.
Samantha M.

Meanwhile, the HER2 expert who I was talking to was telling me about an amazing clinical trial for a drug for HER2 that was looking for people who had not been treated yet. My oncologist didn’t know about that trial, so I brought it up with him and he was kind enough to look into the research, look into the statistics, and weigh the options for me.

He said, “At the end of the day, it’s up to you which one you would like to proceed with, but here are my thoughts.” He was leaning towards traditional chemo and immunotherapy because immunotherapy had foundational success in the long run. The clinical trial was still in its early days in knowing what the outcome would be in the long term.

I also didn’t want to wait. Joining a clinical trial in another hospital involved flying, getting scans again, etc. I wanted to start treatment, so we decided on traditional chemo and immunotherapy and started that within a week.

As weird as it is to say this as a stage 4 cancer patient, chemotherapy and immunotherapy can do wonders.

Response to Treatment

I was responding extremely well and I’m very fortunate that I don’t have that many side effects at all. I have a couple of days of low energy, but other than that, I have been able to live my life, hike, and work.

I spoke to my husband and as weird as it is to say this as a stage 4 cancer patient, chemotherapy and immunotherapy can do wonders. There’s a horrible misconception that chemo and immunotherapy are awful and they don’t do anything. I get very upset about that because it has changed my life and has done amazing things for my body. I haven’t felt this well in years.

Looking back, even though I didn’t have very apparent symptoms, I was tired all the time. I would take naps during the day. I would be exhausted after 10 hours of sleep. I lost five pounds when I’ve never lost weight in my life. There were very subtle signs and if you look at pictures of me, I didn’t look well.

I’m feeling great right now. It’s like a double-edged sword because I have stage 4 cancer, but the chemo and immunotherapy are reducing my cancer burden so much that I feel like normal Samantha again.

Samantha M.
Samantha M.

Having Hope with a HER2 Biomarker

There’s a lot of hope. A HER2 mutation is not an immediate death sentence by any means. We don’t have a targeted therapy right now but that doesn’t mean it’s the end of the line. There are options out there.

Knowing that there are targeted therapies coming out very soon through clinical trials with statistics that show that they work exceptionally well is invaluable.

There’s a lot of hope. A HER2 mutation is not an immediate death sentence by any means.

Words of Advice

You see online that if you eat healthy and you exercise, there’s a very low chance you’re going to get cancer and I don’t like that at all. It makes me very angry and very upset because that makes people who are fit and healthy and doing all the right things think that they’re not going to be touched by cancer.

People must be aware that cancer does not discriminate. It doesn’t care if you’re fit and healthy. It will be in whoever it wants to be and that’s a fact.

Listen to your body. Be in touch with changes. If you have a lump, if you have a weird cough that has continued for months, if you have a weird mole that you’re not sure about, don’t wait.

If your gut is telling you something is wrong and your doctor says it’s fine and not to worry about it, get a second opinion. Push and be that person and get the answers you need to get. You have to advocate for yourself.

Samantha M.

Bayer

Special thanks again to Bayer for its support of our independent patient education content. The Patient Story retains full editorial control.


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Medical Update Article

Conquering Cancer: The Impact of ASCO on Patient Care

Conquering Cancer

The Impact of ASCO on Patient Care

Back to ASCO 2024

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?

Introduction to ASCO: Advancing Cancer Care

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.

Chicago, IL – McCormick Place – 2023 ASCO Annual Meeting – The ASCO Annual Meeting highlights the latest findings in all major areas of oncology. Photo by © ASCO/Matt Herp 2023.

ASCO’s Impact on Cancer Care

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.

Chicago, IL – McCormick Place – 2023 ASCO Annual Meeting – Dr Gregory Roloff presents Abstract 7001 during Hematologic Malignancies?Leukemia Myelodysplastic Syndromes and Allotransplant Oral Abstract Session – Photo by © ASCO/Matt Herp 2023.

The Importance of Cancer Clinical Trials

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.

Chicago, IL – McCormick Place – 2023 ASCO Annual Meeting – Speakers during ASCO Press Briefing – Physicians, researchers, and health care professionals from over 100 countries are attending the 59th ASCO Annual Meeting. Photo by © ASCO/Matt Herp 2023.

Latest Cancer Breakthroughs at ASCO Conferences

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.

Chicago, IL – 2017 ASCO Annual Meeting – Cathy Eng, MD, FACP, discussing Abstract LBA1 during Plenary Session at the American Society of Clinical Oncology (ASCO) Annual Meeting Photo by © ASCO/Rodney White 2017

ASCO’s Role in Addressing the Cost of Cancer Care

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.

Boston, MA – ASCO’s 2021 Quality Care Symposium – Aakash Desai, MPH, MD speaks during Rapid Abstract Session A: Cost, Policy, and Supportive Care at the 2021 Quality Care Symposium at the Boston Marriott Copley Place. Photo by © ASCO/Todd Buchanan 2021

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.

Dr. Shanahan

Past Conference Updates

Categories
Clinical Trials FAQ

The Belmont Report: Protecting People in Clinical Trials

The Belmont Report: Protecting People in Clinical Trials

Clinical trials advance cancer research and help current and future generations find new treatments for disease. However, when patients enroll in a clinical research trial, they want to know that they are safe and that the trial won’t do more harm than good. 

Doctor smiling while holding a stethoscope

Enter the Belmont Report, a set of fundamental ethical principles and guidelines that assist researchers in resolving ethical principles when conducting research involving human subjects. In this article, we look at the history and content of the Belmont Report and its implication on cancer research.

History of the Belmont Report

The Belmont Report was created due to several contributing factors that made the need for a code of ethics in medical research using human subjects essential. 

The extreme human rights violations during World War II, followed by the events of the Tuskegee study, prompted Richard Nixon to create the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. This commission ultimately produced the Belmont Report.

The Nuremberg Code

Following the horrors of World War II and the information unraveled in the Nuremberg Trials, the international scientific community discovered a need for a code of ethics when conducting research on human subjects.

The Nuremberg Code, published in 1947, was created as a guide to satisfy moral, ethical, and legal concepts surrounding human experimentation. The document laid out 10 essential points for conducting ethical research. Amongst other things, the points included the following:

  • Requirement for voluntary consent
  • Qualifications for researchers conducting experiments
  • The importance of ensuring the benefits of an experiment outweigh the risks
  • Participants’ right to terminate the experiment
  • Investigators duty to terminate an experiment if they believe it will result in harm to the subjects

While the Nuremberg Code was a good start for providing ethical guidance in conducting human research, it soon became apparent that further action was needed.

Colorectal Cancer Clinical Trials

“Trials happen in early-stage disease. They can be as a first-line treatment, when someone is first diagnosed, and also with advanced disease, where the goal of the trial is how to improve the standard treatment either by adding new medication or changing medications completely based on data from studies in advanced disease.”

Dr. Cercek | The Latest in Colorectal Clinical Trials

Public Health Services (PHS) Tuskegee Study

From 1932 to 1972, the United States Public Health Service (PHS) conducted a study to observe the effects of syphilis if it remained untreated. During this period, the PHS observed the impacts of syphilis on nearly 400 black men. 

The main problem of the study was that the patients were not informed of the true intent. In fact, they were blatantly lied to as they were told that they would be treated for the disease in return for meals, medical exams, and burial insurance. However, throughout the study, patients were denied access to penicillin, the treatment for syphilis. 

The lack of information provided and disregard for the patients’ well-being led to a class action lawsuit and increased scrutiny of human subject protection policies. 

National Research Act (1974)

The National Research Act of 1974 was passed due to the public attention surrounding the PHS Tuskegee Study. The Act created the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, which was charged with developing a code of ethics and conduct for research involving human subjects.

While the Nuremberg Code provided the guidelines for ethical human subject research, the National Research Act codified those requirements into US law. The National Commission produced the Belmont Report in 1979, which remains one of the most important reports in protecting the safety of human subjects in medical research. 

The 3 Basic Ethical Principles

The main product of the Belmont Report was the publication of three basic ethical principles to help guide and resolve ethical problems surrounding research with human participants. The three principles are:

  • Respect for Persons: All people should be respected. This includes children and individuals who may not be capable of making informed decisions due to mental or physical disabilities.
  • Beneficence: Research should not intentionally harm humans. In addition, researchers should look to maximize the potential benefits of a study and minimize the potential risks.
  • Justice: The benefits and burdens of research should be distributed fairly.

Although the Belmont Report was published almost half a decade ago, its guiding ethical principles still remain relevant today. In the next couple of sections, we will look at how these guiding principles have been applied to the way clinical trials are managed.

“A big part of what we do is help to educate and really clarify what clinical trials are.”

Leah Szumita, Clincal Trial Support Director at The LLS| Watch “What is a Clinical Trial Really?

Applications of the Belmont Report

The three ethical principles are phenomenal foundational ideas; however, they are just that: ideas. Understanding how the idea translates to actual clinical trials is essential for research participants to feel safe agreeing to participate in trials.

Here are a few of the ways that the three principles have been applied to research:

  • Respect for Persons -> Informed Consent: Patients have the right to make the decision to participate or not to participate in a trial. To consent to participate in a trial, potential participants must receive information about the trial, be able to comprehend the impacts of a trial, and voluntarily agree to the trial. All three factors must be present to provide informed consent.
  • Beneficence -> Assessment of Risks and Benefits: Researchers need to thoroughly examine the benefits and potential risks of a study. Without clear supporting evidence that a trial will do more good than harm, the study can’t move forward. 
  • Justice -> Selection of Participants: Researchers are required to implement a fair and equitable method for selecting study participants. When possible, participants should be from a diverse set of backgrounds.

These three applications have become standard practice in conducting research. All three applications should be clearly evident in all trials.

Institutional Safeguards

Researchers can generally be trusted to have the safety and well-being of their patients in mind. However, research and academic institutions have created several fail safes to ensure that patients are well protected. 

Institutional Review Boards

The Institutional Review Board (IRB) is a group specifically formed for the purpose of ensuring that people participating in clinical trials are protected and that all federal laws are followed. Before they are formed, IRBs are approved and overseen by the Office of Human Research Protections. 

Before a clinical trial can start recruiting patients, they must receive approval from an IRB. The trial is then continuously overseen by the IRB to ensure compliance.

Data Safety Monitoring Boards

A Data Safety Monitoring Board (DSMB) is a panel of experts that are typically brought on during a phase III clinical trial. The DSMB observes the progress of a clinical trial and stops it if:

  • It becomes clear the treatment is much better or much worse than the current standard of treatment.
  • There are extreme safety concerns that make it obvious that the risks of the trial outweigh the benefits of the trial.

Clinical Investigators

While both the DSMB and IRB are not directly involved with the study, the clinical investigator, sometimes referred to as the principal investigator, is directly overseeing all aspects of a clinical trial. 

The clinical investigator is responsible for ensuring that all trial participants understand any risks involved with participating in a study and for ensuring their safety throughout the trial. 

“Never think of trials as being exposed to random things. They’re very well thought out. More often than not, you have a high level of reassurance.”

Dr. Rafael Fonseca | The Latest on Multiple Myeloma

Are Clinical Trials Safe?

As a result of the Belmont Report and the resulting events that followed, clinical trials have become much safer for participants. Doctors are required to inform patients of all the potential risks of enrolling in a clinical trial and ensure that the potential benefit of the trial outweighs the risks. 

While it’s impossible to guarantee that a trial will be completely safe, patients can be assured that they’ll have all the information they’ll need to make the decision that is right for them. 

Learn More About Clinical Trials

Sources:

American Cancer Society. Protecting People in Clinical Trials. Accessed at https://www.cancer.org/cancer/managing-cancer/making-treatment-decisions/clinical-trials/what-you-need-to-know/protection-for-study-participants.html on October 15, 2023

Columbia University. Ethics and the IRB. Accessed at https://www.tc.columbia.edu/institutional-review-board/irb-blog/2020/the-history-of-the-belmont-report/#:~:text=The%20Belmont%20Report%2C%20a%20founding,a%20rich%20history%20of%20development.&text=“Good%20judgment%20comes%20from%20experience,experience%20comes%20from%20poor%20judgment.”&text=The%20Institutional%20Review%20Board%20(IRB,for%20research%20with%20human%20subjects on October 15, 2023.

HHS. The Belmont Report. Accessed at https://www.hhs.gov/ohrp/regulations-and-policy/belmont-report/index.html on October 15, 2023

University of North Carolina. Nuremberg Code. Accessed at https://research.unc.edu/human-research-ethics/resources/ccm3_019064/ on October 15, 2023

ERAU. History of Ethics. Accessed at https://erau.edu/-/media/files/university/research/irb-history-of-ethics.pdf on October 15, 2023

FDA. Institutional Review Board Frequently Asked Questions. Accessed on https://www.fda.gov/regulatory-information/search-fda-guidance-documents/institutional-review-boards-frequently-asked-questions October 15, 2023.

Categories
Multiple Myeloma Specialist Rafael Fonseca

Multiple Myeloma Screening | Rafael Fonseca, MD

Multiple Myeloma Screening

Rafael Fonseca, MD
(ASH 2021)

Published March 2022

This image has an empty alt attribute; its file name is Rafael-Fonseca-SQ-1024x1024.png

Dr. Rafael Fonseca shares information about multiple myeloma clinical trials, new therapies, and emerging changes in the standard of care for multiple myeloma patients, following the American Society of Hematology (ASH) 2021 conference,

Dr. Fonseca has been a practicing hematologist for almost three decades, now interim executive director at Mayo Clinic. As a veteran specialist of the myeloma field, he shares his insights on the latest in emerging treatments and clinical trial studies.

The interview has been edited only for clarity.


Studies: iSTOP and PROMISE

The Patient Story: There were two big studies discussed at ASH focused on screening: iSTOP in Iceland, and the PROMISE study led by Dana Farber that started a couple of years ago, which focused on diverse populations. Can you describe the importance of those studies?

Why iSTOP Matters

This [iSTOP] is an incredibly important trial. Their goal was to do the whole screening for the country of Iceland. And what they went about to do was set up a system whereas people would be offered to be screened for the presence of monoclonal proteins. And they have a very robust partnership with the laboratory methodology to be able to test this at a high level and with great precision.

This is where phase III trials meet real world data, and really establishes some very interesting findings.

Dr. Rafael Fonseca

They went about to do a population based study, and at the end of it all, it was very, very large– 75,000 people. This is where phase III trials meet real world data, and really establishes some very interesting findings.

There were three or four key takeaways. One is that we know there’s a small fraction of the population with smoldering multiple myeloma, so they have established that through screening. It’s less than one percent that they estimated, but it’s still measurable. And that is important because as we have clinical trials where people are saying we should think about treating smoldering, we’re going to have to be more and more careful about that.

One of the randomizations was how to approach patients and then what to do afterwards.  What they’re trying to see is if you have an early intervention, and you detect this early, then you can prevent some of the complications.

That’s very important because a myeloma patient who progresses to development of lytic bone lesions, especially if that results in a fracture, or renal problems, can have lifelong consequences. Then, as they live many years now after diagnosis, that’s very undesirable.

It also establishes the baseline for the prevalence of monoclonal gammopathy of undetermined significance (MGUS) in that population. So what we need to do is to think about how this extrapolates. I think there’s a susceptibility according to the various regions, but for what they tried to test, it was a remarkable study.

Why PROMISE Matters

PROMISE is a very large study led by the team of Dr. Ghobrial from Dana-Farber. And they’re able to show higher prevalence than expected for monoclonal gammopathy.  In populations at risk, although the numbers will evolve, the number I keep in my head is about 10%. That’s in people who have family members who have monoclonal gammopathy or individuals of African-American ancestry, who have a higher incidence for this.

I hold the belief that many of us have slightly abnormal plasma cells somewhere in our body because we get exposed so many times through our lifetime that the opportunity for a mistake is actually quite high.

Dr. Rafael Fonseca

The other finding that was remarkable was that they found that a small fraction of patients that have abnormalities that would be a little bit more like a pre-MGUS, and some of those were reported as transient.

Now, there’s no reason to believe that humans don’t have some old clones. We know that for other tumors. So it was only logical that in time it would be found in patients who have things like MGUS. I hold the belief that many of us have slightly abnormal plasma cells somewhere in our body because we get exposed so many times through our lifetime that the opportunity for a mistake is actually quite high.

But you know, the studies are descriptive for the most part right now. But I really commend the efforts of the team of Dr. Ghobrial as well, too, in trying to establish this new baseline.

Takeaways for Current Patients

The Patient Story: What are the takeaways for current patients regarding screening?

You know, there is no agreement at the moment regarding screening strategies or recommendations. And the reason for that is that these are conditions for which we don’t necessarily have treatments that will completely eradicate the process.

You screen for polyps because if you can excise those polyps, then you decrease the risk of colon cancer. But with the bone marrow, it’s very hard to do that because you can’t go in and just pull out the abnormal cells and then leave the rest of the bone marrow.

There is no question that, as time goes by and as the cells grow, there’s a greater likelihood that one might have a complication.

Dr. Rafael Fonseca

However, the question will change as was shown by the iSTOP study, because now the question is, “Can you do something to prevent a complication from happening?” There is no question that, as time goes by and as the cells grow, there’s a greater likelihood that one might have a complication.

So if you detect early, you might not be able to move on fully to the curative approach, although there are some clinical trials that are asking that question. But you might be able to establish a more careful monitoring strategy so that the next time you meet that person, it is for another laboratory testing, and not because the person has been admitted to the hospital with a fracture or with renal failure.

I think with most of the patients we see that have this condition, there’s somewhat surprise findings. You know, they’re going for a physical, and they’re found to have an elevated protein or someone orders a protein electrophoresis for other reasons, and now they know they have it. So we monitor them, but we don’t do this at large.

Genetic Screening

Now we get the question often from family members. “My mom or my dad has myeloma. What can I do to test?” So we give them the names of those tests, but without much information as far as what to do. And I feel like patients and families should know as well that we don’t have the best pathways yet defined, as it’s still early on.

[Testing] is a double-edged sword, because now you know you have it, then that creates a little bit of stress and anxiety. But on the other hand, you can prevent those complications.

Dr. Rafael Fonseca

But for instance, if you were in a family where there’s two or three members who have myeloma, that would be a pretty strong signal that there’s some familial clustering and then the person might want to test. And why not, if they find something to monitor? It’s a double-edged sword, because now you know you have it, then that creates a little bit of stress and anxiety. But on the other hand, you can prevent those complications.

Interestingly, at this meeting, we had a presentation by a team that looked for germline genetic changes that may predispose people to myeloma. They found that about 9% of patients have some genes that potentially could be contributing to the development of myeloma. Again, it’s very early, but that would be another path to explore as well.

Identifying Risk for Black Patients

The Patient Story: With PROMISE, there was a focus on Black patients, and a recognition that the high risk population over 50 years old was twice as likely as the general population to have MGUS. If you are a Black patient, what do you need to know about elevated risk, and do you need to talk to your primary care doctor? 

You know, it could be right, but I don’t think we are ready yet to make recommendations. I think for readers in the audience who may have this question or that concern, it’s a fair request that your doctor does that testing if you are interested. As I mentioned earlier, we don’t have guidelines. I can’t pull them out and say, “This is what needs to be done.”

But I think people rightfully are concerned and would like to know. And the obvious question is, “Why?” And the “why” is so that you can have a good screening strategy. I hope that within the next five to ten years, we will have more specific guidance as far as what to do because again, if we can prevent complications, that would be pretty good.


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Cancer treatments save lives, but they also come with side effects. Hear straight from patients who’ve been treated for cancer - what they experienced and what helped them get through it...

Hair Loss and Regrowth After Chemotherapy

Hear how cancer patients dealt with hair loss after chemotherapy and what some of them used to help growth after that loss...
chemo brain

Chemo Brain: What It Is and How To Cope

Read how cancer patients, caregivers, and coworkers can cope with chemo brain during cancer treatment...

Taxol, Hair Loss & The Inevitable New ‘Do

Why does losing one’s hair cause a waterfall of tears? Read the deeply personal stories of cancer survivors' hair loss and regrowth...
radiation burns

Radiation Burns: How to Cope With Radiation Burns

Read patient testimonies and advice about managing burns from radiation therapy...