Post-Hoc Analysis Evaluates Ruxolitinib Plus Anemia-Supportive Therapies in Myelofibrosis: Pankit Vachhani, MD

In part 1 of an interview conducted after the European Hematology Association 2025 Congress, Pankit Vachhani, MD, associate professor of medicine at the University of Alabama at Birmingham, discusses the current treatment approaches for managing anemia in patients with myelofibrosis, as well as the unmet needs that remain.

Building on this, he outlines the objectives and methodology of his abstract, "Clinical Outcomes in Patients With Myelofibrosis Treated With Ruxolitinib and Anemia Supporting Medications," which he presented on June 13 during the session, "Assessment of Risk and Survival in MPN."

This transcript was lightly edited; captions were auto-generated.

Transcript

For context, can you describe the current treatment options for managing anemia in patients with myelofibrosis? What key evidence gaps remain?

Anemia, first of all, is a big problem in myelofibrosis. It's actually one of the cardinal features of MPNs [myeloproliferative neoplasms], especially myelofibrosis, whereby either patients have it at the time of their diagnosis or they will go on to develop anemia at some point in their treatment journey.

Now, what we have at present is 4 different JAK [Janus kinase] inhibitors [that] are FDA-approved for [the] treatment of myelofibrosis, all in a line-agnostic fashion. The first one of these drugs was ruxolitinib, a JAK1, JAK2 inhibitor approved back in 2011. Since then, we have momelotinib, fedratinib, and pacritinib. These are the 4 inhibitors that are used, but we don't have a drug specifically for anemia management in myelofibrosis. Now, we do have, for example, momelotinib, which is a JAK1, JAK2 inhibitor but also has data that supports its use in patients with myelofibrosis with anemia.

In our present day and age, the guidelines talk about using either supportive care management, like, for example, erythropoietin-stimulating agents (ESAs), like Procrit [Epoetin] or darbepoetin, or other drugs like danazol, sometimes even blood transfusions, or maybe a drug like luspatercept, to manage anemia that is happening with the use of ruxolitinib.

In some other cases, patients may prefer to choose a different JAK1, JAK2 inhibitor, like the ones that we just spoke about. In which case, someone could use momelotinib, or maybe even pacritinib, for their management. That is where the current landscape is.

Now, of course, we don't know [what] some of these combinations of drugs do. For example, even though we've been using ruxolitinib and ESA therapy, we don't have a large data set that supports and tells us what we should expect should we end up using that regimen. Similarly, we don't have a lot of data for some of the other combinations, like with danazol or luspatercept.

To that point, there is a clinical trial of luspatercept in patients requiring transfusions on ruxolitinib therapy called INDEPENDENCE (NCT04717414). That's a large phase 3 clinical trial that is supposed to read out in 2025, [which] may help us guide our decision-making, as well.

Largely speaking, we need more data in this setting. Of course, we also need new drugs so that we can optimize both the myelofibrosis at the JAK-STAT pathway level and also support their anemia, be that with one drug or a combination of drugs.

With that in mind, what were the primary objectives of your study? What methods were used to investigate this?

In our study, which was a post-hoc analysis, the main objective was to evaluate the treatment patterns and also the clinical outcomes of patients with myelofibrosis who [received] treatment with ruxolitinib and either an ESA, an erythropoietin-stimulating agent, or danazol from the large phase 3b JUMP trial (NCT01493414).

What we did was analyze the JUMP database. JUMP, as some of our audience members would know, enrolled [2233 patients] in this large, global, single-arm, open-label, phase 3p expanded-access study. This was done nearly 10 years ago, and maybe slightly even before that. Patients could have gone on this study with a diagnosis of primary or secondary myelofibrosis, and they had to have baseline platelet counts of 50 or more. They were treated with ruxolitinib, 5 to 20 mg, twice daily, based on their baseline platelet count.

For our very specific study, though, which was a post-hoc analysis, what we did was we were interested in only those patients who had baseline anemia, meaning they had to have a hemoglobin [level] less than 12. We paid special attention to those who had hemoglobin [level] less than 10, so that was an important subset for us.

We only took those who had not been on either an ESA or danazol within 3 months of enrollment, but they started 1 of these within 3 months of enrollment and stayed on it for at least 3 months. In a way, this was a study that helped assess patients who were on ruxolitinib and started anemia-supportive medication relatively [recently] so that we could assess what their clinical outcomes were with this combination approach. In terms of the assessments, what we relied on was [the] spleen length response and symptom response using assessment tools, which were done with the overall JUMP database.