Aaron T. Gerds, MD, MS, Associate Professor of Medicine, Deputy Director for Clinical Research at the Cleveland Clinic Taussig Cancer Institute and Medical Director of the Case Comprehensive Cancer Center Clinical Research Office at Cleveland Clinic. In this audio, he speaks about the EHA 2022 abstract MOMENTUM: Phase 3 randomized study of Momelotinib (MMB) versus Danazol (DAN) in symptomatic and anemic myelofibrosis (MF) patients previously treated with a jak inhibitor.
Outline
History
MMB, a new oral ACVR1/ALK2 and JAK1/2 inhibitor, demonstrated clinical activity in the SIMPLIFY trials for MF symptoms, RBC transfusion requirements (anemia), and spleen volume.
Targets
This pivotal phase 3 research compared MMB to DAN on major symptom, anemia, and spleen volume endpoints at 24 weeks in MF patients previously treated with a JAK inhibitor (JAKi) (wks).
Methodologies
Eligibility requirements include: primary or post-ET/PV MF; DIPSS high risk, Int-2, or Int-1; MF Symptom Assessment Form Total Symptom Score (MFSAF TSS) 10; hemoglobin (Hgb) 10 g/dL; prior JAKi for 90 days, or 28 days if RBC transfusions 4 units in 8 wks or Gr 3/4 thrombocytopenia, anemia, or hematoma; palp TSS (22 vs 22), palpable spleen (12 cm vs 12 cm), and RBC units transfused (0, 1-4, and 5+) stratification The JAKi taper and washout took 21 days. Randomization: MMB 200 mg QD + DAN placebo or DAN 600 mg QD plus MMB placebo for 24 weeks, followed by open-label MMB. Assessments: The patient kept a daily eDiary and had his spleen volume measured with an MRI or CT. TSS response (50 percent reduction from baseline [BL]) rate was the primary goal at week 24. Secondary objectives were RBC transfusion independence (TI) rate, splenic response rate (SRR; 25% reduction in volume from BL), change from BL in TSS, SRR (35 percent reduction from BL), and rate of zero transfusions since BL, all examined sequentially at wk 24. All participants provided informed consent.
Outcomes
The 24-week randomized treatment (RT) phase was completed by 94 of 130 (72%) MMB patients and 38 of 65 (58%) DAN patients. Hgb levels were 8.1 (MMB) and 7.9 (DAN) g/dL, and platelets were 97 (MMB) and 94 (DAN) x109/L, respectively. BL TI was 13% (MMB) and 15% (LMB) (DAN). The mean spleen volume in BL patients was 2367 (MMB) and 2288 (DAN) cm3. Prior JAKi was ruxolitinib in 195 patients (100%) and fedratinib in 9 patients (5%); the mean duration of prior JAKi was 134 weeks. All of the primary and secondary endpoints were met (Table). The most common Grade 3 treatment-emergent adverse events (TEAEs) in the RT phase of the research were thrombocytopenia (MMB, 22%; DAN, 12%). (MMB, 8 percent ; DAN, 11 percent ). Gr 3 infections occurred in 15% of MMB patients and 17% of DAN patients. Peripheral neuropathy (PN) occurred in 5% of MMB (all Gr 2) and 2% of DAN (Gr 2) pts during the RT phase, with no patients discontinuing study medication due to PN. Overall, TEAEs caused study drug discontinuation in 18% of MMB and 23% of DAN patients, with significant TEAEs observed in 35% of MMB and 40% of DAN patients during the RT phase. MMB vs DAN showed a trend toward improved OS up to week 24 (HR=0.506, p=0.0719).
Conclusions
MMB was superior than DAN in symptomatic and anemic MF patients for symptom responses, transfusion requirements, and spleen responses, with comparable safety and good survival. MMB may fill a crucial unmet need, especially in MF patients with anemia. NCT04173494.