Momelotinib Demonstrated Superior Responses, Survival to Danazol in Patients With Thrombocytopenic Myelofibrosis

Momelotinib, an oral JAK1/2 and ACVR1/ALK2 inhibitor, was superior to danazol in symptomatic, anemic, and thrombocytopenic myelofibrosis patients for symptom responses, transfusion requirements, and spleen responses, with comparable safety and favorable survival, according to results from a phase 3 trial published in Clinical Lymphoma, Myeloma and Leukemia.

In the double-blinded, phase 3 MOMENTUM study, patients with symptomatic and anemic myelofibrosis who had previously received treatment with a Janus kinase (JAK) inhibitor were randomized on a 2:1 basis to be treated with either 200 mg of momelotinib orally once daily (plus twice daily danazol placebo) or 600 mg of danazol orally twice daily (plus once daily momelotinib placebo) for 24 weeks.

The primary end point was total symptom score (TSS) response (defined as ≥50% reduction from baseline) rate at week 24. Second end points included transfusion independence, splenic response rate of ≥25% volume reduction from baseline, TSS change from baseline, splenic response rate of ≥35% reduction, and rate of 0 transfusions since baseline. A subgroup analysis evaluated patients in this study with baseline platelet counts ≤150 × 10⁹/L.

The TSS response rate was 29.6% for the momelotinib arm and 11.6% in the danazol arm. In the momelotinib arm vs the danazol arm respectively, the TI rate was 32.1% vs 18.6%,the splenic response rate of ≥25% reduction was 39.5% vs 7.0%, TSS change was -10.7 vs -3.8, splenic response rate of ≥35% reduction was 22.2% vs 4.7%, and rate of zero transfusions was 30.9% vs 11.6%. The subgroup 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 momelotinib vs danazol. The efficacy results were found to be consistent with the intent-to-treat analysis set for momelotinib vs danazol.

The most common grade ≥3 treatment-emergent adverse events were thrombocytopenia (31% in the momelotinib arm vs 16% in the danazol arm) and anemia (7% vs 14%). Grade ≥3 bleeding events occurred in 9% of patients in the momelotinib arm and 5% of patients in the danazol arm. Treatment-emergent adverse events lead to discontinuation in 15% of patients being treated with momelotinib and 19% of patients treated with danazol. A trend toward improved overall survival up to week 24 was seen with momelotinib vs danazol (hazard ratio (HR) = 0.490; 95% confidence interval [CI], 0.195 to 1.235). 

Aaron Gerds, MD, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH, and colleagues concluded, “In symptomatic, anemic, and thrombocytopenic [myelofibrosis] patients, [momelotinib] was superior to [danazol] for symptom responses, transfusion requirements, and spleen responses with comparable safety and favorable survival. [Momelotinib] may address a critical unmet need in thrombocytopenic [myelofibrosis] patients.”

Source:

Gerds A, Verstovsek S, Vannucchi A, et al. 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]. Clin Lymph, Myel and Leuk. 2022;22:S340. doi:10.1016/S2152-2650(22)01464-1