EHA 2025 | Survival impact of Hb improvement in MF treated with momelotinib: analyses of SIMPLIFY-1 & MOMENTUM

So, we know that when hemoglobin is less than 10 grams per deciliter, this is a very negative prognostic factor according to all the major prognostic models that we have currently for myelofibrosis. Momelotinib is a new JAK1, JAK2 inhibitor, but also a ACVR1 inhibitor, and it is the only therapy which is currently approved for the treatment of myelofibrosis with splenomegaly symptoms and moderate to severe anemia. So in our study at EHA, we wanted to understand whether achieving hemoglobin greater than 10 could be associated with a prolonged survival, and we also wanted to evaluate the kinetics of hemoglobin improvement during momelotinib therapy. And to this end, we have conducted a sub-analysis of patients from the SIMPLIFY-1 clinical trial who received momelotinib in the front line, and from the MOMENTUM study, who received momelotinib in second line after ruxolitinib failure. And all these patients had a baseline hemoglobin below 10 grams. 

So in the phase three SIMPLIFY-1 trial in JAK inhibitor-naive patients, we observed that 69% of the patients with moderate anemia at baseline, and 50% of patients with severe anemia at baseline achieved hemoglobin greater than 10 by week 24. So the first message is that hemoglobin improvement is more frequent in patients starting momelotinib with a lower degree of anemia. Also, we have observed that hemoglobin improvement was faster for the patients with a lower degree of anemia, with a mean time to improvement of 1.2 months for the moderate subgroup and 2.1 months for the severe anemic subgroup. 

So if you look at the results in the second line in the Phase III MOMENTUM trial with JAK inhibitor-experienced patients, we observed quite similar results. For example, 47% of patients with moderate anemia at baseline and 24% of patients with severe anemia at baseline achieved hemoglobin greater than 10 by week 24. And the mean time to improvement was shorter for the patients with moderate anemia, one month, compared to 1.7 months in the patients with severe anemia. 

But overall, what is the clinical significance of achieving hemoglobin higher than 10 in the first six months of momelotinib therapy? And to answer this question, we observed that the overall survival from treatment start was actually numerically longer for the patients who achieved the hemoglobin greater than 10 by week 24 with momelotinib, both in the course of JAK inhibitor naive and in the course of JAK inhibitor experienced patients. 

So finally coming to the take-home messages. It is very important to state that baseline anemia severity and also JAK inhibitor exposure influenced the probability and the timing of achieving hemoglobin greater than 10 grams per deciliter with momelotinib. So to achieve the best results, it is important to start momelotinib earlier when anemia is not severe and to use momelotinib in the frontline setting, since JAK inhibitor-naive patients with a moderate anemia are more likely and faster to achieve hemoglobin greater than 10. And this is very important because achieving a hemoglobin greater than 10 is a very powerful positive prognostic factor for overall survival. So overall this highlights how anemia improvement should be the most important treatment goal and the potential benefits for early anemia interventions with momelotinib.

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