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- Title
MOMENTUM: Phase 3 Randomized Study of Momelotinib (MMB) versus Danazol (DAN) in Symptomatic and Anemic Myelofibrosis (MF) Patients Previously Treated with a JAK Inhibitor.
- Authors
Mesa, Ruben; Gerds, Aaron; Vannucchi, Alessandro; Al-Ali, Haifa Kathrin; Lavie, David; Kuykendall, Andrew; Grosicki, Sebastian; Iurlo, Alessandra; Yeow Tee Goh; Lazaroiu, Mihaela; Egyed, Miklos; Fox, Maria Laura; McLornan, Donal; Perkins, Andrew; Sung-Soo Yoon; Gupta, Vikas; Kiladjian, Jean-Jacques; Donahue, Rafe; Kawashima, Jun; Verstovsek, Srdan
- Abstract
Background: MF is a rare bone marrow cancer characterized by fibrosis, abnormal blood cell production, and dysregulated JAK/STAT signaling.1,2 Clinical manifestations include anemia, constitutional symptoms, and splenomegaly, which can negatively impact patient quality of life.3-5 Although approved JAK inhibitors (JAKi) may improve symptoms and splenomegaly, none actively treat anemia and some may exacerbate it; the efficacy of other agents currently used to manage anemia in MF (eg, DAN) is short-lived.6-8 MF-associated anemia is driven by chronic inflammation and due in part to resultant hyperactive ACVR1 signaling and elevated hepcidin levels.6 MMB is unique among JAKi in that it inhibits not only JAK1 and JAK2 to drive symptom and spleen improvements but also ACVR1 to drive anemia benefits, including increased serum iron and hemoglobin levels.9 In the SIMPLIFY trials, MMB was associated with improvements in symptoms, splenomegaly, and transfusion burden in both JAKi-naive and JAKi-experienced patients with MF.10,11 The pivotal phase 3 MOMENTUM study of MF patients previously treated with a JAKi tested MMB versus DAN on key symptom, anemia, and splenic end points. Methods: Eligibility: Primary or post-ET/PV MF; DIPSS Background: MF is a rare bone marrow cancer characterized by fibrosis, abnormal blood cell production, and dysregulated JAK/STAT signaling.1,2 Clinical manifestations include anemia, constitutional symptoms, and splenomegaly, which can negatively impact patient quality of life.3-5 Although approved JAK inhibitors (JAKi) may improve symptoms and splenomegaly, none actively treat anemia and some may exacerbate it; the efficacy of other agents currently used to manage anemia in MF (eg, DAN) is short-lived.6-8 MF-associated anemia is driven by chronic inflammation and due in part to resultant hyperactive ACVR1 signaling and elevated hepcidin levels.6 MMB is unique among JAKi in that it inhibits not only JAK1 and JAK2 to drive symptom and spleen improvements but also ACVR1 to drive anemia benefits, including increased serum iron and hemoglobin levels.9 In the SIMPLIFY trials, MMB was associated with improvements in symptoms, splenomegaly, and transfusion burden in both JAKi-naive and JAKi-experienced patients with MF.10,11 The pivotal phase 3 MOMENTUM study of MF patients previously treated with a JAKi tested MMB versus DAN on key symptom, anemia, and splenic end points. Methods: Eligibility: Primary or post-ET/PV MF; DIPSS response (24.6% vs 9.2%), TI (30.8% vs 20.0%), SRR25 (40.0% vs 6.2%), TSS change (-9.36 vs -3.13), SRR35 (23.1% vs 3.1%), and zero transfusions (35.4% vs 16.9%). Most common grade ≥3 treatment-emergent adverse events (TEAEs) in RT were thrombocytopenia (MMB, 22%; DAN, 12%) and anemia (MMB, 8%; DAN, 11%). TEAEs led to study drug discontinuation in 18% of MMB and 23% of DAN patients in RT. A trend toward improved survival up to week 24 was seen with MMB versus DAN (hazard ratio, 0.506; P = .0719). Conclusions: In symptomatic and anemic MF patients, MMB was superior to DAN for symptom responses, transfusion requirements, and spleen responses with comparable safety and favorable survival. MMB may improve MF patient care and quality of life by addressing a critical unmet need, particularly in patients with anemia.
- Publication
Journal of Oncology Navigation & Survivorship, 2022, Vol 13, Issue 11, p377
- ISSN
2166-0999
- Publication type
Academic Journal