Momelotinib vs. ruxolitinib in myelofibrosis patient subgroups by baseline hemoglobin levels in the SIMPLIFY-1 trial

Leuk Lymphoma. 2024 Jul;65(7):965-977. doi: 10.1080/10428194.2024.2328800. Epub 2024 Mar 19.

Abstract

A key hallmark of myelofibrosis is anemia, which ranges from mild to severe based on hemoglobin levels. To more clearly define outcomes with the Janus kinase (JAK) 1/JAK2/activin A receptor type 1 inhibitor momelotinib by anemia severity, we performed a descriptive post hoc exploratory analysis of the double-blind, randomized, phase 3 SIMPLIFY-1 study (NCT01969838; N = 432, JAK inhibitor naive, momelotinib vs. ruxolitinib); subgroups were defined by baseline hemoglobin: <10 (moderate/severe), ≥10 to <12 (mild), or ≥12 g/dL (nonanemic). Spleen and symptom results were generally consistent with those previously reported for the intent-to-treat population. In anemic subgroups, momelotinib was associated with higher rates of transfusion independence and reduced/stable transfusion intensity vs. ruxolitinib. No new or unexpected safety signals were identified. Overall, momelotinib provides spleen, symptom, and anemia benefits to JAK inhibitor-naive patients with myelofibrosis regardless of baseline hemoglobin level, and greater anemia-related benefits vs. ruxolitinib in patients with hemoglobin <12 g/dL.

Keywords: Anemia; hemoglobin; momelotinib; myelofibrosis; ruxolitinib; transfusion independence.

Publication types

  • Randomized Controlled Trial
  • Clinical Trial, Phase III
  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Anemia / diagnosis
  • Anemia / etiology
  • Benzamides / therapeutic use
  • Double-Blind Method
  • Female
  • Hemoglobins* / analysis
  • Hemoglobins* / metabolism
  • Humans
  • Janus Kinase 1 / antagonists & inhibitors
  • Janus Kinase 2 / antagonists & inhibitors
  • Janus Kinase 2 / genetics
  • Male
  • Middle Aged
  • Nitriles*
  • Primary Myelofibrosis* / diagnosis
  • Primary Myelofibrosis* / drug therapy
  • Protein Kinase Inhibitors / therapeutic use
  • Pyrazoles* / therapeutic use
  • Pyrimidines* / therapeutic use
  • Treatment Outcome

Substances

  • Pyrimidines
  • ruxolitinib
  • Pyrazoles
  • Nitriles
  • Hemoglobins
  • N-(cyanomethyl)-4-(2-((4-(4-morpholinyl)phenyl)amino)-4-pyrimidinyl)benzamide
  • Benzamides
  • Protein Kinase Inhibitors
  • Janus Kinase 1
  • Janus Kinase 2