EHA 2025 | Impact of dual spleen response & transfusion independence in momelotinib-treated patients with MF

So SIMPLIFY-1 is the only head-to-head trial of JAK inhibitors and this trial compared ruxolitinib, the JAK1/2 inhibitor that has been the standard of care for many years, with momelotinib, which is the new JAK1, JAK2, but also ACVR1 inhibitor, which is approved for the patient with MF, splenomegaly symptoms and moderate to severe anemia. And it was already published that in the overall cohort and also in subgroup of patients with a baseline hemoglobin less than 10, momelotinib is not inferior to ruxolitinib in achieving the spleen volume response by week 24. 

In our analysis at EHA 2025, we wanted to explore more. We wanted to see whether the spleen response was confirmed across different subgroups defined by, for example, by age, risk or platelet count, baseline spleen volume. And from this analysis, I think that we must take two main clinical messages. 

First, we have observed that spleen volume response is not influenced by the degree of splenomegaly. So, momelotinib is not inferior to ruxolitinib, also in the patient with a large spleen. And second, we have observed that spleen volume response is indeed influenced by the platelet count. In the patients with a baseline platelet count less than 200, the spleen volume response is observed in 39% of patients treated with momelotinib compared to only 17% in the patients treated with ruxolitinib. And if you look at the patients with a platelet count less than 100, the difference is striking. The spleen volume response rate is 46% with momelotinib and zero with ruxolitinib. And also we have observed that spleen responses with momelotinib are durable with a median duration of approximately three years. And I think this is a completely new information which really helps us in our clinical practice because it demonstrates that once obtained, the spleen response may be stable over the time. 

But actually, we also wanted to explore the probability and also the clinical significance of achieving a dual response, including spleen and transfusion independence response. So we analyzed patients with baseline anemia and we observed that the rates of dual spleen and transfusion independence responses at week 24 were significantly higher with momelotinib, 27%, compared to only 7% with ruxolitinib. Importantly, these dual responses, spleen and transfusion independence, were higher with momelotinib across all subgroups defined by factors like age, risk score, platelet count, baseline spleen volume. And when we looked more closely at spleen and transfusion independent response in the patient with platelet count less than 200, the rates were higher with momelotinib, 19% versus 13% with ruxolitinib. And so I think that here we have another important clinical message. While the spleen response rates may be higher with ruxolitinib, if my patients have a platelet count greater than 200, this often comes to the expense of an increased transfusion requirements. So if we improve splenomegaly with ruxolitinib, we generally also acquire anemia. 

But what is the impact of transfusion independent response or of dual responses on the patient prognosis? Because this is what matters really for our patients. So we performed the Kaplan-Meier analysis of an overall survival according to the response status at week 24. And for the patients who were both transfusion independent and achieved the spleen response at 24, the survival was longer compared to the patient who had no response at all. And very importantly, survival was comparable whether the patient were transfusion-independent alone or had a dual response. 

So final take-home messages. Momelotinib may achieve higher rates of dual spleen and anemia response in patients with baseline anemia. Transfusion independence seems to be more strongly associated with overall survival in momelotinib-treated patients compared to spleen volume reduction. And so I think that there is a growing body of evidence here that transfusion independence in patients with anemia should be the great priority over spleen volume reduction if we want to optimize the long-term outcomes. 

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