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Momelotinib: Impact on transfusion dependence and QoL in MF

By Jen Wyatt Green

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Jean-Jacques KiladjianJean-Jacques Kiladjian

Nov 8, 2024

Learning objective: After watching this expert opinion video, learners will be able to cite key data from phase III trials of momelotinib in patients with MF and anemia and recall the implications of these findings for treatment algorithms in patients with MF.


Test your knowledge! Take our quick quiz before and after you read this article to find out if you improved your knowledge. Results help us to improve content and continually provide open-access education.

Question 1 of 2

In the MOMENTUM trial, what was the difference in the rate of transfusion independence achieved by patients after 24 weeks in the momelotinib vs danazol arms, respectively?

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B

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D

The MPN Hub was pleased to speak with Jean-Jacques Kiladjian, Professor of Clinical Pharmacology at Université Paris Cité, Paris, France. We asked, What is the impact of momelotinib on transfusion dependence and quality of life (QoL) in myelofibrosis (MF)? 

Momelotinib: Impact on transfusion dependence and QoL in MF

Kiladjian highlights the reduction of transfusion dependence and symptoms for patients with MF and anemia treated with momelotinib. He reviews key data from the phase III SIMPLIFY-1 (NCT01969838), SIMPLIFY-2 (NCT02101268), and MOMENTUM (NCT04173494) studies, and the implications of these findings for treatment algorithms in patients with MF.

Key learnings 

  • Anemia is present in one-third of patients at diagnosis with MF, with over half becoming anemic within 1 year of diagnosis.
  • Anemia is a key negative prognostic factor in various scoring systems, highlighting its clinical significance.
  • Patients with MF-related anemia often respond poorly to existing treatments such as erythropoietin-stimulating agents.
  • While ruxolitinib offers efficient symptom control in MF, it may induce anemia and transfusion dependence due to off-target effects.1 In the SIMPLIFY-1 and SIMPLIFY-2 studies, momelotinib demonstrated improvements in splenomegaly, symptoms, and anemia.1,2
  • The phase III MOMENTUM study was designed to confirm the differentiated clinical benefits of momelotinib vs danazol in anemic patients with symptomatic MF previously treated with a JAKi.
  • According to the primary publication, in the MOMENTUM study (N = 195):
    • The primary endpoint was the Myelofibrosis Symptom Assessment Form (MFSAF) total symptom score (TSS) response rate at Week 24 (≥50% reduction in mean MFSAF TSS over the 4 weeks prior to the end of Week 24 vs baseline).2
    • Around 30% of patients receiving momelotinib achieved transfusion-independence after 24 weeks vs 20% of patients in the danazol arm.2
    • 22% of patients receiving momelotinib achieved a ≥35% reduction in spleen volume (SVR35) from baseline at Week 24 vs 3% of patients in the danazol arm.2
    • While momelotinib and danazol both induced rapid increases in mean hemoglobin levels, momelotinib induced greater increases in hemoglobin maintained over time vs danazol; and hemoglobin levels increased further in patients in the danazol group upon crossing over to momelotinib.2
  • A potential future treatment algorithm may have ruxolitinib as first-line treatment for the majority of patients, with momelotinib as first-line treatment in patients with anemia at baseline or who are transfusion-dependent at diagnosis and as a second-line treatment for patients who develop anemia or become transfusion-dependent during JAKi treatment.
  • Anemia and transfusion dependence are a burden for patients with MF; in MOMENTUM, momelotinib was associated with improvement in physical function and overall QoL compared with danazol in patients with MF.2


This educational resource is independently supported by GSK. All content is developed by SES in collaboration with an expert steering committee; funders are allowed no influence on the content of this resource.


References