MPN-483 Thrombocytopenic Myelofibrosis (MF) Patients Previously Treated With a JAK Inhibitor in a Phase 3 Randomized Study of Momelotinib (MMB) versus Danazol (DAN) [MOMENTUM]

Aaron Gerds, Srdan Verstovsek, Alessandro Vannucchi, Haifa Kathrin Al-Ali, David Lavie, Andrew Kuykendall, Sebastian Grosicki, Alessandra Iurlo, Yeow Tee Goh, Mihaela Lazaroiu, Miklos Egyed, Maria Laura Fox, Donal McLornan, Andrew Perkins, Sung Soo Yoon, Vikas Gupta, Jean Jacques Kiladjian, Rafe Donahue, Jun Kawashima, Ruben Mesa

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Abstract

Background: MMB, an oral JAK1/2 and ACVR1/ALK2 inhibitor, was evaluated (vs DAN) in a pivotal phase 3 study of MF patients previously treated with a JAK inhibitor (JAKi). This subgroup analysis evaluated MOMENTUM patients with baseline platelet counts ≤150 × 109/L. Methods: Eligibility: Primary or post-ET/PV MF; DIPSS high risk, Int-2, or Int-1; total symptom score (TSS) ≥10; hemoglobin <10 g/dL; prior JAKi ≥90 days, or ≥28 days if RBC transfusions ≥4 units in 8 weeks or Grade 3/4 thrombocytopenia, anemia, or hematoma; palpable spleen ≥5 cm; platelets ≥25 × 109/L. JAKi taper/washout ≥21 days. Randomization 2:1 to MMB 200 mg or DAN 600 mg QD (+ placebo) for 24 weeks. Primary endpoint: TSS response (≥50% reduction from baseline) rate at week 24. Secondary endpoints at week 24: transfusion independence (TI) rate, splenic response rate (SRR; ≥25% volume reduction from baseline), TSS change from baseline, SRR (≥35% reduction), and rate of zero transfusions since baseline. Results: Mean baseline TSS: 29 MMB, 26 DAN, hemoglobin: 8.1 MMB, 7.8 DAN g/dL, and platelets: 74 × 109/L MMB, 73 × 109/L DAN. Efficacy results are consistent with the ITT analysis set for MMB vs DAN, respectively: TSS response rate (29.6% vs 11.6%), TI rate (32.1% vs 18.6%), SRR ≥25% (39.5% vs 7.0%), TSS change (-10.7 vs -3.8), SRR ≥35% (22.2% vs 4.7%), and rate of zero transfusions (30.9% vs 11.6%). Most common grade ≥3 TEAEs were thrombocytopenia (MMB, 31%; DAN, 16%) and anemia (MMB, 7%; DAN, 14%); grade ≥3 bleeding events: 9% MMB, 5% DAN. TEAEs leading to study drug discontinuation: 15% MMB, 19% DAN. A trend toward improved overall survival up to week 24 was seen with MMB vs DAN [HR (95% CI)=0.490 (0.195, 1.235)]. Analyses of patients with baseline platelets <100 × 109/L (N=100) and baseline platelets <50 × 109/L (N=31) show similar efficacy, safety, and survival profiles for MMB vs DAN. Conclusions: In symptomatic, anemic, and thrombocytopenic MF patients, MMB was superior to DAN for symptom responses, transfusion requirements, and spleen responses with comparable safety and favorable survival. MMB may address a critical unmet need in thrombocytopenic MF patients. NCT04173494.

Original languageEnglish
Pages (from-to)S340
JournalClinical Lymphoma, Myeloma and Leukemia
Volume22
DOIs
StatePublished - Oct 2022
Externally publishedYes

Keywords

  • JAK inhibitor
  • MPN
  • Phase III
  • anemia
  • momelotinib
  • myelofibrosis
  • thrombocytopenia

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