In patients with thrombocytopenic myelofibrosis who were symptomatic and anemic, momelotinib (MMB) demonstrated superiority relative to danazol (DAN) for symptom responses, transfusion requirements, and spleen responses, according to research presented at the 2022 ASCO Annual Meeting.
The findings are from MOMENTUM, a pivotal phase 3 study comparing the efficacy and safety of MMB vs DAN in patients with MF who are symptomatic and anemic and were previously treated with a JAK inhibitor (JAKi). The presented analysis evaluated patients with baseline platelet counts of ≤150 x 109/L (ClinicalTrials.gov Identifier: NCT04173494).
Patients were eligible for the study if they had primary or post-essential thrombocythemia/polycythemia vera MF; high, intermediate-2, or intermediate-1 risk disease according to the Dynamic International Prognostic Scoring System; an MF Symptom Assessment Form Total Symptom Score (TSS) ≥10; hemoglobin <10 g/dL; prior JAKi (for ≥90 days or ≥28 days if receiving red blood cell transfusions of ≥4 units within 8 weeks; or Grade 3/4 thrombocytopenia, anemia, or hematoma); a palpable spleen of ≥5 cm; and a platelet count of ≥25 x 109/L.
Patients were randomly assigned (2:1) to receive MMB (200 mg daily) plus DAN placebo or DAN (600 mg daily) plus MMB placebo for 24 weeks. The primary endpoint was TSS response (≥50% reduction from baseline) rate at week 24. Key secondary endpoints at week 24 included RBC transfusion independence (TI) rate, splenic response rate (SRR; ≥25% reduction in volume from baseline), change from baseline TSS, SRR (≥35% reduction from baseline) and rate of zero transfusions from baseline.
A total of 124 patients were evaluated in this portion of the study, 81 in the MMB arm and 43 in the DAN arm. Of those, 74% of patients in the MMB arm and 58% of those in the DAN arm completed the 24-week randomized treatment (RT) phase. The median baseline TSSs were 29 in the MMB arm and 24 in the DAN arm. The median hemoglobin level was 7.9 g/dL in the MMB arm and 8.0 g/dL in the DAN arm. The median platelet counts were 67 x 109/L in the MMB arm and 64 x 109/L in the DAN arm.
The 24-week TSS response rate was 29.6% in the MMB arm and 11.6% in the DAN arm, a difference of 18.0 (95% CI, 0.7-31.5). The TI rate was 32.1% in the MMB arm and 18.6% in the DAN arm, a difference of 13.5 (95% CI, -3.9 to 28.5). The SRR of ≥25% was 39.5% in the MMB arm and 7.0% in the DAN arm, a difference of 32.5 (95% CI, 15.3-45.4). The TSS change from baseline was -10.7 in the MMB arm and -3.8 in the DAN arm, a difference of -7.0 (95% CI, -11.7 to -2.2).
The SRR of ≥35% was 22.2% in the MMB arm and 4.7% in the DAN arm, a difference of 17.6 (95% CI, 2.3-29.1). The zero transfusion rate was 30.9% in the MMB arm and 11.6% in the DAN arm, a difference of 19.2 (95% CI, 2.3-32.8). There was a trend toward improved overall survival up to week 24 in patients receiving MMB compared with those receiving DAN (hazard ratio, 0.49; 95% CI, 0.195-1.235).
The most common grade ≥3 treatment-emergent adverse events during the RT phase were thrombocytopenia (MMB, 31%; DAN, 16%) and anemia (MMB, 7%; DAN, 14%). Grade ≥3 bleeding events were reported in 9% of the MMB arm and 5% of the DAN arm. TEAEs led to discontinuation in 15% of the MMB arm and 19% of the DAN arm.
Disclosure: This research was supported by Sierra Oncology, Inc. Please see the original reference for a full list of disclosures.
Gerds AT, Verstovsek S, Vannucchi A, et al. Thrombocytopenic myelofibrosis (MF) patients previously treated with a JAK inhibitor in a phase 3 randomized study of momelotinib (MMB) versus danazol (DAN) [MOMENTUM]. Presented at ASCO 2022; June 3-7, 2022. Abstract 7061.