Rapid Readouts: SIMPLIFY-1 and SIMPLIFY-2 Trials

Ruben Mesa, MD, discusses data from the following presentation:

• Transfusion Independence Is Associated With Improved Overall Survival in Myelofibrosis Patients Receiving Momelotinib (Mesa R, EHA 2021, Abstract S202)
  • The objective of this study is to report data from patients with myelofibrosis treated with the JAK1, JAK2, and ACVR1/ALK2 inhibitor momelotinib in the SIMPLIFY-1 and SIMPLIFY-2 trials:
    • SIMPLIFY-1: momelotinib (MMB) vs ruxolitinib (RUX) in JAK inhibitor-naïve patients (NCT01969838)
    • SIMPLIFY-2: MMB vs best available therapy (BAT; RUX in 88% of patients) in patients with prior JAK inhibitor (ruxolitinib) therapy (NCT02101268)
  • Background:
    • Transfusion independence (TI) response rates were higher for MMB compared with BAT/RUX in both SIMPLIFY-1 (67% vs 49%) and SIMPLIFY-2 (43% vs 21%).
    • The week 24 TI response was higher in patients randomly assigned to MMB vs RUX, regardless of baseline anemia, platelet count, or transfusion status.
    • In SIMPLIFY-1, median overall survival (OS) was found to be 53.1 months in the RUX to MMB crossover arm compared with the MMB to MMB arm, where OS was not reached. In SIMPLIFY-2, median overall survival was 37.5 months in BAT/RUX to MMB arm vs 34.3 months in MMB to MMB arm.
  • Results:
    • SIMPLIFY-1: 3-year survival in MMB TI responders was 80% compared with 50% in MMB TI nonresponders (HR, 0.30; P< .0001); similar results are found for patients with anemia who are week 24 MMB TI responders.
    • SIMPLIFY-2: Patients randomized to MMB who were TI responders at week 24 show a trend toward better OS compared with TI nonresponders (HR, 0.52; P= .0652).