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ASCO 2024 | The impact of JAK2 allele burden on the efficacy of JAK inhibitors in myelofibrosis
Prithviraj Bose, MD, The University of Texas MD Anderson Cancer Center, Houston, TX, discusses the varying efficacy of JAK inhibitors in patients with myelofibrosis (MF) who have either cytopenic or proliferative disease. Ruxolitinib and fedratinib show greater effectiveness in patients with proliferative disease, characterized by preserved blood counts and a higher JAK2 allele burden. In contrast, momelotinib and pacritinib are more effective for those with cytopenic disease, who generally have less favorable outcomes. Dr Bose highlights that these differences are primarily based on clinical phenotype rather than JAK2 allele burden. This interview took place during the 2024 American Society of Clinical Oncology (ASCO) Meeting in Chicago, IL.
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Transcript
JAK2 allele burden has been around for a long time, but we have not really understood it very well, at least in the sense of how to tailor therapy according to it. Now there is some evidence emerging in this regard. Now, in 2016, just to put things in perspective, Doctor Barosi had published that ruxolitinib works best in patients who have an allele burden of 50% or greater. Since then, we’ve learned a lot about these two concepts of cytopenic or myeloid depletive MF and myeloproliferative MF as being sort of a two ends of a spectrum with everything in between...
JAK2 allele burden has been around for a long time, but we have not really understood it very well, at least in the sense of how to tailor therapy according to it. Now there is some evidence emerging in this regard. Now, in 2016, just to put things in perspective, Doctor Barosi had published that ruxolitinib works best in patients who have an allele burden of 50% or greater. Since then, we’ve learned a lot about these two concepts of cytopenic or myeloid depletive MF and myeloproliferative MF as being sort of a two ends of a spectrum with everything in between. And we’ve learned that at least a sort of, conceptually that, there are certain drugs that work better for cytopenic patients and certain drugs that work better for proliferative patients.
So in general, I would say that ruxolitinib and fedratinib, are drugs that work better in the proliferative patients who have, you know, preserved blood counts, larger spleens, a higher JAK2 allele burden, speaking of that, fewer other mutations and generally a more favorable outcome. Whereas you have the patients on the other end who are cytopenia smaller spleens, lower JAK2 allele burdens many other mutations, worse outcome. These are the patients where pacritinib and momelotinib may have more of a role. I think that is mostly where we are right now. I don’t think we choose therapy based on the allele burden per se. And on this note, I’ll actually mention an abstract that was presented at ASCO by our group this morning. And we showed that it is not really about the allele burden per se. It is more about the clinical phenotype that distinguishes these patients.
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