ASH 2025 | Ruxolitinib plus CDK4/6 inhibitor abemaciclib in previously treated myelofibrosis: Phase I results

This was a, or this is an ongoing phase one study that we’re running at Memorial Sloan-Kettering Cancer Center in New York as well as at Yale. And this is a study that involves patients with myelofibrosis that have been previously treated with Ruxolitinib and have a suboptimal response to ruxolitinib monotherapy, which is defined as either persistent symptom burden or residual splenomegaly, despite at least 12 weeks of treatment with ruxolitinib. And the rationale for the addition of a CDK4-6 inhibitor, in our case abemaciclib, is that mutations in the JAK-STAT pathway lead to upregulation of the cell cycle, so combined inhibition of the cell cycle at different levels, at the level of the JAK receptor, as well as further downstream CDK4-6 could have synergistic effects. 

So in this phase one trial, patients were treated with a fixed dose of ruxolitinib of 10 or 15 milligrams twice a day, and then increasing doses of abemaciclib. What we presented at ASH is the primary analysis of nine patients, so three patients at each dose level. And we did see, first of all, that this was a well-tolerated treatment. There were no dose-limiting toxicities or serious adverse events identified in any of the patients. As expected, diarrhea was the most common side effect, which is a known side effect of abemaciclib. And then we had anemia and thrombocytopenia, which can be seen with both agents as well as with the disease itself. However, those were usually low-grade – there were two patients with grade 3 anemia and one patient with grade 3 neutropenia. However, no patient discontinued treatment because of adverse events. Among the subset of patients that was available for response, we did see a reduction in spleen volume in five out of six patients with a spleen volume reduction of at least 25%, and half of the patients had a spleen volume reduction of at least 35%. We also saw an improvement in absolute symptom score in five out of six evaluable patients. So this is very encouraging. And in my opinion, we did see objective evidence of efficacy among patients with advanced myelofibrosis in a treatment that was fairly well tolerated. The study is ongoing. We’re looking at other molecular response parameters, looking at changes in bone marrow pathology. And I’m very delighted that this combination is proceeding to a phase two trial to really study the efficacy more.

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