Oncology

Myelofibrosis

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Risk Stratification in Myelofibrosis

expert roundtables by Aaron T. Gerds, MD, MS; Stephen T. Oh, MD, PhD; Raajit K. Rampal, MD, PhD
Overview
<p>Risk stratification in myelofibrosis provides prognostic information that can help inform clinical decision making. In this article, our experts delve into the nuances and current limitations of risk stratification tools and their potential for use in guiding the decision to transplant.</p>
How do you use risk stratification tools in the management of myelofibrosis?
“The question is: What do we do with the information acquired from risk stratification tools? An important point is that this information is not telling you how to treat the patient, but rather it is telling you the relative potential risk of the patient’s disease progressing.”
— Raajit K. Rampal, MD, PhD

We have a lot of different tools for risk stratification in myelofibrosis, and it is similar to the iPhone in that it feels like there is a new one every year. The question is: What do we do with the information acquired from risk stratification tools? An important point is that this information is not telling you how to treat the patient, but rather it is telling you the relative potential risk of the patient’s disease progressing. That, to me at least, can inform the discussion about the consideration of a transplant, and this is what these types of tools are useful for.

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How well do these risk stratification tools do this? One way to think about it is by understanding the amount of concordance between the tools. However, although there is concordance, there is also discrepancy, and I think that this is where the problem lies. It is not unusual to have a patient whose Dynamic International Prognostic Scoring System (DIPSS) risk score tells you one thing while their Mutation-Enhanced International Prognostic Scoring System (MIPSS70) score tells you something very different. Determining which tool we should use in this circumstance and how to adjudicate scoring differences is difficult to resolve and likely requires further refinement of the tools using validated biomarkers. This would give us a more predictive benefit for a given individual patient with myelofibrosis, although we are not quite there yet.

“Whichever risk stratification tool or collection of tools we are using, the biggest determination in terms of treatment decision making in myelofibrosis has been and remains whether we should push for transplant in those who might be eligible.”
— Stephen T. Oh, MD, PhD

Whichever risk stratification tool or collection of tools we are using, the biggest determination in terms of treatment decision making in myelofibrosis has been and remains whether we should push for transplant in those who might be eligible. That said, of course, there is also informational content provided by risk stratification tools in terms of overall outlook, expected survival, and transformation risk that I think some patients with myelofibrosis really are craving and want to have a detailed discussion about. However, other patients really do not want or need that and are instead more focused on what we are going to do. From that standpoint, I do not find risk stratification really vital.

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I think that, in the future, it would be ideal if we could develop more precise, patient-specific, personalized medicine risk stratification schemes to guide our treatment, but that is entirely dependent on having therapies that can act in a patient-specific manner. I think that we are getting to at least the concept of that being achievable (eg, with therapies such as those specifically directed at CALR mutations and next-generation JAK2 inhibitors in development). So, while we are getting closer to that potentially becoming a reality, historically, we have not had those kinds of options in our treatment armamentarium.

“I think that risk stratification tools are helpful for determining who should be going to transplant, but they do not really help guide decisions regarding other treatments. . . .”
— Aaron T. Gerds, MD, MS

I think that risk stratification tools are helpful for determining who should be going to transplant, but they do not really help guide decisions regarding other treatments that have largely similar efficacy in patients with myelofibrosis. There are no large-enough differences between the available JAK inhibitors to justify saying that we want to use risk stratification in some way to determine treatment.

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As we develop new therapies that work differently from or in complementary ways to JAK inhibitors, and as the effective use of combination therapies moves forward, I think that we will be able to develop new risk stratification tools. They might help us determine whether we would want to use a particular JAK inhibitor for an individual patient, and, if so, as a single agent or as a part of combination therapy. My hope is that these tools will begin to evolve once we have more therapies available and that they can be used to identify specific treatments for specific patients more accurately and precisely. I think that this will come with time as we develop new therapies.

References

Duminuco A, Nardo A, Giuffrida G, et al. Myelofibrosis and survival prognostic models: a journey between past and future. J Clin Med. 2023;12(6):2188. doi:10.3390/jcm12062188

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Gagelmann N, Mora B, Branzanti F, et al. Personalized transplant decision making for myelofibrosis in the era of molecular genetics and JAK Inhibition. Blood. 2024;144(suppl 1):245. doi:10.1182/blood-2024-210804

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Kramer F, Mullally A. Antibody targeting of mutant calreticulin in myeloproliferative neoplasms. J Cell Mol Med. 2024;28(5):e17896. doi:10.1111/jcmm.17896

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Luque Paz D, Gagelmann N, Benajiba L, et al. Role of molecular alterations in transplantation decisions for patients with primary myelofibrosis. Blood Adv. 2025;9(4):797-807. doi:10.1182/bloodadvances.2024014368

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Michaelis LC. Risk stratification in myelofibrosis: the quest for simplification. Haematologica. 2017;102(1):2-3. doi:10.3324/haematol.2016.158865

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Scott BL, Gooley TA, Sorror ML, et al. The Dynamic International Prognostic Scoring System for myelofibrosis predicts outcomes after hematopoietic cell transplantation. Blood. 2012;119(11):2657-2664. doi:10.1182/blood-2011-08-372904

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Sharma N, Loscocco GG, Gangat N, et al. When and how to transplant in myelofibrosis – recent trends. Leuk Lymphoma. 2025;66(3):359-377. doi:10.1080/10428194.2024.2422835

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Tefferi A. Primary myelofibrosis: 2023 update on diagnosis, risk-stratification, and management. Am J Hematol. 2023;98(5):801-821. doi:10.1002/ajh.26857

Aaron T. Gerds, MD, MS

    Associate Professor of Medicine
    Deputy Directory for Clinical Research
    Cleveland Clinic Taussig Cancer Institute
    Medical Director
    Case Comprehensive Cancer Center Clinical Research Office
    Case Western Reserve University
    Cleveland, OH

Stephen T. Oh, MD, PhD

Associate Professor and Co-Chief
Division of Hematology
John T. Milliken Department of Medicine
Washington University School of Medicine
St. Louis, MO

Raajit K. Rampal, MD, PhD

Associate Member
Director, Myeloproliferative Neoplasms Program
Director, Center for Hematologic Malignancies
Memorial Sloan Kettering Cancer Center
New York, NY

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