Evaluating the Current Myelofibrosis Treatment Paradigm

At the Society of Hematological Oncology 2025 Annual Meeting, Prithviraj Bose, MD, delivered a presentation titled “Individualizing Treatment Selection for MF,” where he dissected the nuance of selecting treatments for patients with myelofibrosis.

When asked about what he believed to be the most significant takeaways from the discussion, he spoke about his excitement regarding interferons, although he acknowledged it was still early to make data-driven comments about them. He also spoke to the current state of FDA-approved JAK inhibitors, of which there are 4 inhibitors.

The 4 approved inhibitors are ruxolitinib (Jakafi), which has a survival benefit but must be dosed appropriately; momelotinib (Ojjaara), which is useful when a patient has myelofibrosis where anemia is predominant; pacritinib (Vonjo), which also has an anemia benefit, albeit to a lesser degree than momelotinib; and fedratinib (Inrebic), which is useful for patients who have progression on ruxolitinib and are in need of a second-line agent.

Bose is a professor in the Department of Leukemia in the Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center.

Transcript:

In early myelofibrosis—prefibrotic as well as clinically early overt myelofibrosis—I’m excited about interferons, and I’m excited to see what they will bring, but these are early days. I do not think I can make a data-driven comment on that yet. For anemia, there are some exciting therapies being developed; there are drugs like DISC-0974 and elritercept, and we know luspatercept-aamt [Reblozyl] works. We have made some good advances in anemia-directed therapies for patients where anemia is the predominant clinical problem.

When we come to the JAK inhibitors; that’s where the meat is. For the JAK inhibitors, in the context of this quick interview, I’ll just make a few brief points. Ruxolitinib, we must remember, has a survival benefit. It is a great drug that has a survival benefit, but it has to be dosed appropriately. If we are looking at doses lower than 15 mg twice a day—in fact, to be a purist, maybe even less than 20 mg twice a day—we are probably not giving the optimal dose of ruxolitinib. We have to remember that it has a survival benefit, but we do not get the same efficacy across doses. For low-dose ruxolitinib, in my view, with anything less than 15 mg twice a day, we may not be doing the best for our patients there. Now we have alternatives.

In that context, [we have] momelotinib and pacritinib. I go to momelotinib when it is an anemia-predominant picture. Although pacritinib also has some anemia benefit, I think momelotinib has more of a benefit in that regard. Going back to the point I just made, you can dose those drugs at full doses mostly, regardless of blood counts. That is where there could be an advantage over ruxolitinib, where the dose is being constrained by the cytopenia.

Finally, just one quick word about fedratinib. I like it for patients who have [progression on] ruxolitinib, need a second-line agent, and perhaps have significant splenomegaly symptoms but also have preserved blood counts. It’s not a drug for patients with very low blood counts. That area belongs more to pacritinib and momelotinib. But fedratinib in the second line—I don’t use it in the first line—is a really good drug for spleen and symptoms when you have blood counts that are relatively robust.

Reference

Bose P. Individualizing treatment selection for MF. Presented at: Society of Hematological Oncology 2025 Annual Meeting; September 3-6, 2025; Houston, TX.