Dr Raajit Rampal Highlights Emerging Therapies in MPNs

Interferons have been used for decades to treat myeloproliferative neoplasms (MPNs), and new emerging therapies, such as the Janus kinase (JAK) inhibitor ruxolitinib, are expanding the therapeutic armamentarium, said Raajit Rampal, MD, PhD, hematologic oncologist, associate attending physician, Memorial Sloan Kettering Cancer Center.

This transcript has been lightly edited.

What is the importance of interferons as a treatment for MPNs, and what role do they play?

Interferons have been used now for decades in MPNs, and they demonstrate clinical efficacy, certainly in essential thrombocytopenia, in polycythemia vera, and there is data for prefibrotic myelofibrosis.¹ Now there are a number of different interferons. There were interferons that were given 3 times a week, and pegylated interferon, which is what we use most often, and now there's ropeginterferon, which is every 2 weeks as a treatment.

What the interferons can do, for sure, is that they can reduce blood counts. So, for people with the polycythemia or with essential thrombocytopenia, we can get a reduction in the blood counts in the majority of patients. What is also interesting is that—and as has been known now for a number of years—the allele burden, particularly of JAK2, can decrease over time with the treatment with interferons, which at least would suggest to us that you may be depleting part of the clone that causes the disease. So, there are certainly a number of important clinical benefits of interferons, but even potentially biological effects.

Beyond interferons and hydroxyurea, what other important treatment options are there for patients with MPNs and how are they used?

I think there are a lot of emerging therapies, which is exciting, right? We're past where we were in terms of our therapeutic armamentarium. JAK inhibitors clearly have made a huge mark on MPNs. For polycythemia vera, ruxolitinib was approved as a second-line therapy after hydroxyurea. The data continues to get stronger and stronger for ruxolitinib in polycythemia vera, where there's clearly a superiority in terms of hematocrit control and spleen size control for patients who had been on hydroxyurea previously. It also seems like it is certainly a very effective drug to control symptom burden in our polycythemia vera patients.

There are studies ongoing in Europe right now—there was data presented at the American Society of Hematology annual meeting this year about upfront treatment.² So I think that there's more to be learned there, as well. JAK inhibitors have also been trialed in essential thrombocytopenia with the data today being somewhat equivocal. But clearly ruxolitinib, in particular, has activity in that setting. It's just a question of “will it rise eventually to the level of meeting regulatory approval?” But there's no question that there is activity of JAK inhibitors in essential thrombocytopenia.

And then, of course, in myelofibrosis, we now have 4 approved JAK inhibitors with the last coming last September.³ In that particular group of MPNs where there's the biggest unmet need, there have been some really important gains with the advent of new JAK inhibitors.

References

1. Vachhani P, Mascarenhas J, Bose P, et al. Interferons in the treatment of myeloproliferative neoplasms. Ther Adv Hematol . 2024:15:20406207241229588. doi:10.1177/20406207241229588

2. Koschmieder S, Isfort S, Teichmann LL, et al. Firstline treatment with ruxolitinib versus best available therapy in patients with polycythemia vera: pre-specified interim analysis of the randomized phase 2b Ruxobeat clinical trial of the German Study Group for Myeloproliferative Neoplasms (GSG-MPN). Blood. 2023;142(Supp 1):619. doi:10.1182/blood-2023-173225

3. McNulty R. FDA approves momelotinib for myelofibrosis with anemia. The American Journal of Managed Care®. September 15, 2023. Accessed March 22, 2024. https://www.ajmc.com/view/fda-approves-momelotinib-for-myelofibrosis-with-anemia