Latest Updates in Diagnosis and Risk Stratification of Myelofibrosis
Expert Roundtable Part 1
Expert Roundtable Part 1
In this expert roundtable series, Firas El Chaer, MD, University of Virginia Comprehensive Cancer Center, Charlottesville, Virginia, leads a panel discussion on new updates and strategies in myelofibrosis treatment with Raajit K Rampal, MD, Memorial Sloan Kettering, New York, New York, and Lindsay A M Rein, MD, Duke University Medical Center, Durham, North Carolina.
In part 1 of the roundtable, the experts discuss the latest research in diagnosis and risk stratification of myelofibrosis.
Transcript:
Firas El Chaer, MD: Welcome to Oncology Learning Network. My name is Firas El Chaer. I'm a medical oncologist and hematologist at the University of Virginia. I specialize in myeloid disorders, particularly myeloproliferative neoplasms.
Tonight, I'll be moderating our discussion on myelofibrosis. I am joined today by a distinguished panel of experts. Would each one like to introduce themselves and tell us a bit about each of your roles? We'll start with Dr. Rein.
Lindsay A M Rein, MD: Good evening. Thank you for having me. I really appreciate this opportunity. Always up for a great conversation. My name is Lindsay Rein. I am an associate professor at Duke University Health. I see patients again with myeloproliferative neoplasms [MPNs] and focus specifically on that. As part of my role here, my research interests really are in clinical trials and bringing novel therapies to patients and so I run a program here of trials for patients with MPNs across the spectrum.
Dr El Chaer: Fantastic. And Dr Rampal?
Raajit K Rampal, MD: Hi. It's great to be with both of you for this discussion. I'm Raajit Rampal. I direct the Myeloproliferative Neoplasm program at MSK. I'm a physician scientist and work both in preclinical drug development, but also take care of MPN patients and conduct clinical trials in MPNs.
Dr El Chaer: Thank you both. I'm going to talk a little bit about how our discussion will flow. Today we're going to focus on myelofibrosis. We're going to start with risk stratification. Then we're going to dedicate some time for the frontline therapy for myelofibrosis. Then we'll talk a little bit about relapse refractory, and of course we'll talk about the recent studies that have been presented at ASH 2024 with what's exciting in the field.
I would want to say when I finished my fellowship, myelofibrosis was a disease that was interesting, but I guess in the past 5 years, it has really become much more interesting with a lot of new pathways that we have discovered and a lot of drugs that we can use in this particular disease and offer for our patients.
But maybe we can start with Dr. Rein in the very beginning. When a patient with myelofibrosis comes to your clinic, there has been a lot of risk certification models. What do you use, which one do you deploy in your clinic to decide how you're going to approach your patient population?
Dr Rein: I think you hit the nail on the head with what you started with, in saying that there's been so much developed over the course of the past, really 5 years. I think what we've come to realize is how heterogeneous myelofibrosis is as a disease. It's not just one size fits all anymore and that reflects in all of the different scoring systems that have been created to help risk stratify patients. Whereas before, we used to use more standard scoring systems, the DIPSS [Dynamic International Prognostic Scoring System], the DIPSS Plus, a lot of those are still used within the context of clinical trials.
I think a lot of folks have done a lot of really phenomenal work to incorporate molecular diagnostics and a lot more information to help stratify patients. Now we're looking at scoring systems for patients pre-transplant. We've got scoring systems post-transplant, we've got scoring systems for primary MF, secondary MF, dynamic.
For me, when patients come to clinic, I really first take a look at the patient and decide which scoring system I should at least start to branch into. Does the patient have primary MF where I'm going to be thinking about those types of scoring systems, or do they have a secondary MF where I can apply something like the MYSEC [Myelofibrosis Secondary to PV and ET] scoring system and really think about that from that perspective?Then I look and see what data we have available for that patient, what data we can gather, and more specifically the molecular based data, so the karyotype data or molecular diagnostics.
My personal preference, I think based on a lot of data that's coming out and being presented is to use the scoring systems like the MIPSS [Mutation-Enhanced International Prognostic Scoring System] to really incorporate some of those molecular markers because there's a lot of data now suggesting that those are really important and really do matter in terms of the disease biology. Those are some of the things that I think about as we're applying scoring systems.
Dr El Chaer: For Dr Rampal, I'm going to list them out, all these scores and you tell me how do you approach your patient population. We start with the DIPSS. DIPSS Plus, MIPSS70, MIPSS70 version 2, and lately it’s the GIPSS [Genetically Inspired Prognostic Scoring System], and then we have the MYSEC-PM. Which one do you actually use in your clinic as compared to Dr Rein's approach?
Dr Rampal: We're going to get to the point where we have more scoring systems than MF patients. It is interesting, right, because there's a couple of considerations. One is, the biggest consideration is, do you have the data to use a specific model, right? One thing that's often problematic is cytogenetics. For whatever reason, we don't always get great cytogenetics when we do the marrow from these patients. We don't always have that information, which is necessary for something like DIPSS Plus or for MIPSS70 or version 2 of MIPSS70. But my preference is, I do think that on the genetic level, you learn a lot from having cytogenetics and from having molecular genetics.
My preference is always to use the MIPSS or the DIPSS Plus, which does include cytogenetics. It's important for people also to realize, and this analysis has been done, that the risk stratifications don't necessarily always agree with each other that there is, you can have given set of variables that yields somebody who is perhaps maybe low or intermediate risk in DIPSS, but with MIPSS, they actually get up scored because of their genetics.
That's always something we have to keep in the back of our minds, that none of these are a perfect tool and that there is a lot of overlap, but not entirely. Perhaps the more information you have, the better. That may point you towards using tools like the MIPSS that have more variables taken into account.
Dr Rein: Oddly enough, this is a perfectly timed question. There was a review article published in Blood within the past couple weeks actually creating an algorithm looking at which scoring system should be used and how do we decide. It's very interesting, right along the lines of what you said, the break points really are age, so greater or less than 70, and whether or not the karyotype data is available. That really flows nicely along with that particular point.
Dr El Chaer: One thing to add is when we're looking at these scores and making decisions, especially for example, stem cell transplant or something else, you have to take this score that was used in that particular study that showed that particular outcome. I think it's hard a little bit to extrapolate if a study was based on a DIPSS score and then you move to a MIPSS in your clinic. Yes, you can extrapolate, but we have to be careful when doing these comparisons.