Tag Archives: disease modification

Exploring Possibilities in Disease Modification in MPNs

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October 25, 2024

Author(s): Mary Caffrey

Treatment of myeloproliferative neoplasms (MPNs) has historically focused on delaying or avoiding transformation to acute myeloid leukemia (AML) as well as symptom relief and improving quality of life; strategies addressed thrombosis or enlarged spleen both with therapy and with nonpharmacological strategies such as smoking cessation or encouraging patients to lose weight.

Although these strategies were associated with improving life expectancy, they did not measure disease modification through molecular responses that signal survival benefits, in the way that trials do with AML and chronic myeloid leukemia (CML).

Claire N. Harrison, MD, FRCP, FRCPath | Image credit: Guy’s and St Thomas

Now, in an essay appearing in HemaSphere, a publication of the European Hematology Association (EHA), investigator Claire N. Harrison, MD, FRCP, FRCPath, of the Department of Haematology, Guy’s and St Thomas NHS Foundation Trust, asks whether the study and treatment of MPNs is ready for a new era with new end points, with data that show how survival benefits are biologically linked to changes in the spleen, reduction in fibrosis, or other responses.

The challenge, Harrison writes, is that the requirements will be different from today’s standards. “These data should hopefully influence a paradigm shift for the regulatory agencies and the field toward a focus instead of disease modification, but this will certainly require data extending beyond the recent standard of 24 weeks,” she writes.

In the perspective piece, “Are we ready for disease modification in myeloproliferative neoplasms?” Harrison notes that a dramatic shift that came with arrival of Janus kinase (JAK) inhibitor–based therapy for patients with myelofibrosis (MF) who could not receive a stem cell transplant. Therapy shows the capacity to reduce spleen size and symptoms. “Both of these facets of MF do probably reflect underlying pathophysiology and, furthermore, spleen size reduction has been shown to correlate with overall survival advantage.”

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Dr Raajit Rampal Discusses Disease Modification and Emerging Therapies in Polycythemia Vera

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Laura Joszt, MA

Achieving a disease-modifying therapy for polycythemia vera might require adjusting the end points in a study needed for a drug to be approved, said Raajit Rampal, MD, PhD, hematologic oncologist, associate attending physician, Memorial Sloan Kettering Cancer Center.

Transcript

Currently, there are no disease-modifying treatments in polycythemia vera, but it is being explored. What might such a therapy look like?

If we talk about disease modification, the first question is, what do you mean by disease modification? I think, what we would want is for our patients to live the longest and fullest life, free of the symptoms or burdens of their disease. To me, that is the sort of working definition of disease modification. From there, one can try to come up with biological definitions of things like depleting the stem cell, which are important things. But keeping this on a patient level, what we want for our patients [is a life free of disease burden]. How do we think about therapies that address those issues?

Part of it is a regulatory conundrum in the sense that studies have to meet certain end points for drugs to get approved, but the way we study the drugs is relative to the definitions of the end points that make the drugs successful. In many cases, [the end point is asking] are you controlling the hematocrit adequately? That’s one of the major things in polycythemia vera. But in order to really try to get at the question of disease modification, we’ve got to think about changing the end points of our studies to reflect that.

What are the things that are going to best correlate with the idea that you aren’t keeping patients free of the catastrophic consequences of their disease, like blood clots, like [disease] turning into leukemia or myelofibrosis? Are you controlling the patient’s symptoms to an adequate degree? Those are the things that I think are fundamental. But we’ve got to change the end points of our studies to really get at that.

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