Rapid Readouts: Updated Results From the Phase 3 SIMPLIFY-1 Trial

Jean-Jacques Kiladjian, MD, PhD, discusses data from the following presentation:

• Improved Transfusion Independence Rates for Momelotinib vs Ruxolitinib in Anemic JAKi Naïve Myelofibrosis Patients are Independent of Baseline Platelet or Transfusion Status (Kiladjian, EHA 2021, EP1081)
• The objective of this study is to report transfusion independence results from the SIMPLIFY-1 trial (NCT01969838) in JAK inhibitor–naïve patients with myelofibrosis who were treated with momelotinib (MMB) vs ruxolitinib (RUX).
  • Phase 3, double-blind trial with 1:1 randomization to MMB or RUX (N = 432)
  • MMB is an inhibitor of JAK1, JAK2, and ACVR1/ALK2; RUX is a JAK1 and JAK2 inhibitor
  • Previously reported results:
    • Week 24 (W24) transfusion independence (TI) response rate: 67% on MMB vs 49% on RUX
    • Median overall survival: 53 months in the RUX arm, not reached in the MMB arm
  • Results
    • Treatment with MMB resulted in higher TI rates vs RUX in all patient subsets with baseline (BL) hemoglobin (Hgb) ≤ 14 g/dL, and in all subsets defined by BL platelets (PLTs) and by BL transfusion status.
    • W24 TI rate by BL Hgb:
      • < 8 g/dL: 29% MMB vs 18% RUX
      • < 10 g/dL: 47% MMB vs 27% RUX
      • < 12 g/dL: 62% MMB vs 37% RUX
      • ≤ 14 g/dL: 67% MMB vs 46% RUX
      • > 14 g/dL: 64% MMB vs 89% RUX
    • W24 TI rate by BL PLTs
      • < 150 x 109/L: 62% MMB vs 43% RUX
      • < 300 x 109/L: 68% MMB vs 48% RUX
      • ≥ 300 x 109/L: 63% MMB vs 51% RUX
    • W24 TI rate by BL transfusion status
      • TI: 81% MMB vs 62% RUX
      • Transfusion requiring (neither transfusion dependent [TD] nor TI): 53% MMB vs 31% RUX
      • TD: 30% MMB vs 17% RUX
  • Conclusions
    • Data suggest that an MMB-mediated TI response at week 24 is associated with a survival advantage.
    • These data support the potential benefit of MMB’s ACVR1/ALK2 inhibitor activity in addition to inhibiting JAK1 and JAK2.