Myeloid Lymphoid Neoplasms (MLN)

Srdan Verstovsek, MD, PhD

March 2022

Myeloid lymphoid neoplasms affect an extremely small group of people. Srdan Verstovsek, MD, PhD with MD Anderson estimates that number is a few hundred in the U.S. every year. Watch as he describes one of the most exciting drug developments has happened for MLN patients.

What are myeloid lymphoid neoplasms (MLNs)?

The Patient Story: Thank you so much for that. We’re going to wrap with this, really. You had said a revolutionary, I think it was the word. So it’s exciting to end on this a small population of myeloid lymphoid neoplasms or MLNs with very exciting news coming out. So what was that?

Dr. Serge Verstovsek: Ok, so a very small group of patients with myeloproliferative neoplasms, which sometimes may also have at the same time, which appears like lymphoma, myeloproliferative neoplasms and lymphoma together. That’s why they’re called myeloid and lymphoid neoplasms; it’s a mixed bag. This type of patient is not very common at all.

Genetic abnormality → FGFR

Some of them have a genetic abnormality that we discovered is the driving force behind it. A genetic abnormality is the activation of a certain gene. The gene activates the protein gene, makes proteins right, and this protein is called FGFR that’s the abbreviation fibroblast growth factor. It’s a protein FGFR.

New drug: pemigatinib

Now we have a pill that can inhibit FGFR and eliminate the disease. Can you believe it? That has not existed in the past. This is a very deadly condition. Myeloid/lymphoid neoplasms with FGFR.

Life expectancy is a year-and-a-half. The only way to secure the patients may be some intensive chemotherapy and do the transplant if you can. With the pill, you have a very, very high rate of elimination of the disease.

This was the best of ASH presentations, one of few because it’s altering the life of these people. Unbelievable.

Do patients still need to undergo a transplant?

We still want people to go to transplant because we don’t know, is this going to work forever or what? But it has extreme efficacy with just one daily pill for patients with FGFR myeloid/lymphoid neoplasms .

Now how do you recognize these people? The patients, that’s the key. Usually when we analyze the bone marrow of the patients, we look at how this looks:

• Is it normal abnormal size, shape, and colors?
• You look at the genes, mutations in our genes.
• We also look at the chromosomes. Chromosomes are things like structures inside the cells that carry genes. And it happens that this condition can be recognized by looking at the chromosomes. Every single patient has an abnormality in chromosome eight.

8p11 Syndrome or 8p11 Disease

Now, maybe that’s too much to take, but 8p11 is the code. People call it 8p11 syndrome if you like. 8p11 disease. When this chromosomal abnormality is seen, that is an indication of the FGFR driven disease. So looking at the chromosomes, which is the standard bone marrow type of a test, and seeing 8p11 abnormality in chromosomes identify these patients. And you give them that pill, and it’s a beautiful story after that. This was the best of ASH presentations, one of few because it’s altering the life of these people. Unbelievable.

Follow-up of people in the study?

The Patient Story: That is incredible. Do you know how long the follow-up was of people in the study?

Dr. Serge Verstovsek: The longest one is actually my patient. The number one patient in the study is four years now. The patient was told to have a life expectancy of a year-and-a-half before coming, and it’s four years without any evidence of the disease whatsoever. We still tell him, you should probably go to transplant.

I don’t really know whether this is going to work for 10 or 20 years. I don’t know what’s going to happen tomorrow, but he’s a young gentleman, and he says, no, it’s working four years so far. I don’t want to do anything but continue to take the pill, so others are following someday to do the transplants and did not. We’ll see what happens, but it’s altering for many. It’s amazing.

When will pemigatinib be FDA approved?

The Patient Story: It’s life-changing. It’s a game-changer. How much? I mean, obviously, this takes more study before it goes to the masses, even though this is a smaller population. How much more? I mean, this is safe.

Dr. Serge Verstovsek: Because it’s such efficacy that you don’t see often. There is no need for any further studies. I would suspect that next year, the company behind this drug will apply for approval just on the sheer evidence of amazing results.

And after all, we are not talking about an extraordinary number of patients to study it further would kind of. But why? Unnecessary delay in having the pemigatinib available for these people with 8p11 syndrome. Maybe a few hundred patients like this are seen in the United States a year.

MLN looks different in patients

The Patient Story: That was my next question. So you said a few hundred so really, truly a very small group of people. Ok. What are some of the presentations, I know you can study the chromosome at the chromosomal level, but are there different presentations in terms of symptoms or something?

Dr. Serge Verstovsek: Yes because it’s mixed. Some people have enlarged lymph nodes, and people say, oh, you have lymphoma. Some people have even acute leukemia, either acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL).

Some people have just normal MPN, high white cell count, and high platelets. You think it’s maybe polycythemia vera, but it’s not. You do the bone marrow testing. You do the chromosomal analysis. Analyses of chromosomes, which are standard. You see this abnormality there, and you need to remember, hey, this is not normal. What is this all about? And then you click and say, oh my god, I can cure that.

Dr. Serge Verstovsek: Imagine that we talked about this 15 years ago or even 10 years ago, they would not much talk. The first-ever medication approved for any of the MPN was ruxolitinib 10 years ago, and then about five years ago, the same medication for PV.

Now you have fedratinib for myelofibrosis, you have ropeg for PV and you have all these phase three studies. Unbelievable.

So I invite everybody to join in the efforts to get many more drugs approved, make all these conditions as chronically, chronically possible as I explain. If we cannot cure it, hopefully, we will. But if we can, let’s make it just livable forever.

Landscape of the emerging treatments for myeloproliferative neoplasms (MPNs)

The Patient Story: That’s incredible. That’s a great note to end on. Dr. Verstovsek, I really appreciate your time. Is there anyone last line you want to say to people in terms of the landscape of the emerging treatments for myeloproliferative neoplasms?

Dr. Serge Verstovsek: Imagine that we talked about this 15 years ago or even 10 years ago, they would not much talk. The first-ever medication approved for any of the MPN was ruxolitinib 10 years ago, and then about five years ago, the same medication for PV.

Now you have fedratinib for myelofibrosis, you have ropeg for PV and you have all these phase three studies. Unbelievable. So I invite everybody to join in the efforts to get many more drugs approved, make all these conditions as chronically, chronically possible as I explain. If we cannot cure it, hopefully, we will. But if we can, let’s make it just livable forever.

The Patient Story: Thank you again so much. Really appreciate your expertise and your time to explain this to patients and their caregivers. Dr. Verstovsek hoped to have another conversation with you soon where we have another hour of new treatments and therapies and drugs to talk about. So thank you.

Dr. Serge Verstovsek: Thank you. It was real. Great pleasure. Wonderful discussion. Hopefully very helpful to everybody.

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