Momelotinib Superior to Danazol in Symptomatic and Anemic Myelofibrosis Patients Previously Treated With JAK Inhibitor

Momelotinib improved symptom responses, transfusion requirements, and spleen responses in symptomatic and anemic myelofibrosis patients previously treated with a JAK inhibitor when compared with danazol with comparable safety and favorable survival, according to the phase 3 MOMENTUM study.  Momelotinib, an oral JAK1/2 and ACVR1/ALK2 inhibitor previously “showed clinical activity in the myelofibrosis SIMPLIFY trials,” wrote Ruben Mesa, Mays Cancer Center at UT Health San Antonio MD Anderson, San Antonio, Texas, and colleagues.

The pivatol, phase 3 MOMENTUM trial enrolled 195 patients with primary or post-essential thrombocythemia/polycythemia vera myelofibrosis who had previously been treated with a  JAK inhibitor (100% with ruxolitinib; 5% with fedratinib). Patients were randomized on a 2-to-1 basis to receive either momelotinib 200 mg  plus placebo once a day (n = 130) or danazol 600 mg plus placebo once a day (n = 65) for 24 weeks. Patients were stratified based on total symptom score (TSS), palpable spleen, and red blood cell units transfused. The primary end point was TSS response (≥50% reduction from baseline) rate at week 24. Secondary end points were transfusion independence (TI) rate, splenic response rate (SRR; ≥25% volume reduction from baseline), TSS change from baseline, SRR (≥35% reduction) and rate of 0 transfusions since baseline. 

Of the total randomized patients 72% in the momelotinib group finished treatment, vs 58% in the danazol group. The mean baseline TSS was 28 for patients in the momelotinib group and 26 for danazol group.

The study met all of the primary and key secondary end points. The TSS response rate was 24.6% vs 9.2% in the momelotinib and danazol groups respectively, and the TSS change was -9.36 in the momelotinib group and -3.13 in the danazol group. The TI rate was 30.8% in the momelotinib group vs 20.0% in the danazol group. The SRR of ≥25% reduction was 40.0% vs 6.2% and the SRR of 35% reduction was 23.1% vs 3.1%, respectively. The rate of zero transfusions from basline was 35.4% vs 16.9%, respectively.

The most common grade ≥3 treatment-emergent adverse events were thrombocytopenia (22% in the momelotinib group vs 12% in the danazol group) and anemia (8% vs 11%). Treament-emergent adverse events led to discontinuation in 18% of patients treated with momelotinib and 23% of patients treated with danazol. There was a trend toward improved survival up to week 24 seen with momelotinib vs danazol (hazard ratio [HR] = 0.506, P = .0719). 

“In symptomatic and anemic [myelofibrosis] patients, [momelotinib] was superior to [danazol] for symptom responses, transfusion requirements, and spleen responses, with comparable safety and favorable survival,” the study authors concluded, adding, “Momelotinib may address a critical unmet need, particularly in [myelofibrosis] patients with anemia.”

Source:

Mesa R, Gerds A, Vannucchi A, et al. MPN-478 MOMENTUM: Phase 3 randomized study of momelotinib (MMB) versus danazol (DAN) in symptomatic and anemic myelofibrosis (MF) patients previously treated with a JAK inhibitor. Clin Lymphoma Myeloma Leuk. 2022;22:S339-S340. doi:10.1016/S2152-2650(22)01463-X