Overall survival in the SIMPLIFY-1 and SIMPLIFY-2 phase 3 trials of momelotinib in patients with myelofibrosis

Ruben Mesa, Claire Harrison, Stephen T. Oh, Aaron T. Gerds, Vikas Gupta, John Catalano, Francisco Cervantes, Timothy Devos, Marek Hus, Jean Jacques Kiladjian, Ewa Lech-Maranda, Donal McLornan, Alessandro M. Vannucchi, Uwe Platzbecker, Mei Huang, Bryan Strouse, Barbara Klencke, Srdan Verstovsek

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Janus kinase inhibitors (JAKi) approved for myelofibrosis provide spleen and symptom improvements but do not address anemia, a negative prognostic factor. Momelotinib, an inhibitor of ACVR1/ALK2, JAK1 and JAK2, demonstrated activity against anemia, symptoms, and splenomegaly in the phase 3 SIMPLIFY trials. Here, we report mature overall survival (OS) and leukemia-free survival (LFS) from both studies, and retrospective analyses of baseline characteristics and efficacy endpoints for OS associations. Survival distributions were similar between JAKi-naïve patients randomized to momelotinib, or ruxolitinib then momelotinib, in SIMPLIFY-1 (OS HR = 1.02 [0.73, 1.43]; LFS HR = 1.08 [0.78, 1.50]). Two-year OS and LFS were 81.6% and 80.7% with momelotinib and 80.6% and 79.3% with ruxolitinib then momelotinib. In ruxolitinib-exposed patients in SIMPLIFY-2, two-year OS and LFS were 65.8% and 64.2% with momelotinib and 61.2% and 59.7% with best available therapy then momelotinib (OS HR = 0.98 [0.59, 1.62]; LFS HR = 0.97 [0.59, 1.60]). Baseline transfusion independence (TI) was associated with improved survival in both studies (SIMPLIFY-1 HR = 0.474, p = 0.0001; SIMPLIFY-2 HR = 0.226, p = 0.0005). Week 24 TI response in JAKi-naïve, momelotinib-randomized patients was associated with improved OS in univariate (HR = 0.323; p < 0.0001) and multivariate (HR = 0.311; p < 0.0001) analyses. These findings underscore the importance of achieving or maintaining TI in myelofibrosis, supporting the clinical relevance of momelotinib’s pro-erythropoietic mechanism of action, and potentially informing treatment decision-making.

Original languageEnglish (US)
Pages (from-to)2261-2268
Number of pages8
JournalLeukemia
Volume36
Issue number9
DOIs
StatePublished - Sep 2022

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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