Dr Jain on the Role of JAK Inhibition in Polycythemia Vera and Myelofibrosis - Episode 4

Dr Jain on Persisting Gaps in Defining Disease Modification in Polycythemia Vera and Myelofibrosis

October 27, 2025

Akriti G. Jain, MD, detailed the current unmet needs in polycythemia vera and myelofibrosis, including how to define disease modification.

EP. 1: Dr Jain on the Role of Ruxolitinib in Polycythemia Vera and Myelofibrosis

EP. 2: Dr Jain on Treatment Decision-Making With JAK Inhibitors in Myelofibrosis

EP. 3: Dr Jain on Considerations for Sequencing JAK Inhibitors in Myelofibrosis

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EP. 4: Dr Jain on Persisting Gaps in Defining Disease Modification in Polycythemia Vera and Myelofibrosis

“Right now, the only cure we have for any stem cell or myeloid disorder is a stem cell transplant. Is it possible for us to cure these or modify the natural history of these diseases without a stem cell transplant? That's a big unmet need.”

Akriti G. Jain, MD, a hematologist and medical oncologist at the Cleveland Clinic, detailed the unmet needs that remain in the myeloproliferative neoplasms landscape, particularly regarding JAK inhibition in patients with polycythemia vera and myelofibrosis.

A significant unmet need in polycythemia vera and myelofibrosis is determining what is considered disease modification, which is often a point of discussion at most conferences, Jain began. More research is needed to identify whether disease modification depends on driving the JAK2 allele burden down, or even the CALR or MPL, based on the present mutations, she explained. Specifically, in polycythemia vera, common mutations include JAK2 V617F or JAK2 exon 12 to 15 mutations, she noted. Conversely, in myelofibrosis, frequently observed mutations comprise JAK2, CALR, and MPL, she added. Therefore, it has not been established whether disease modification means driving the allele burden down, the reversal of fibrosis, or the decrease in cytokine or inflammatory hormone levels, she emphasized.

Furthermore, more work needs to be done until combination therapies can help bridge the gap in polycythemia vera and myelofibrosis, Jain continued. The only potential cure for stem cell or myeloid disorders remains a stem cell transplant, she noted. However, another significant need is whether it’s possible to cure or alter the diseases without requiring a stem cell transplant, along with getting patients safely to transplant, she stated. Additionally, essential questions to be addressed include how much spleen shrinkage is needed, and whether patients should continue receiving a JAK inhibitor is necessary after receiving a stem cell transplant.