Findings from the phase 3 MOMENTUM trial presented at the 2022 ASCO Annual Meeting demonstrate the superior efficacy of momelotinib vs danazol for symptomatic and anemic patients with myelofibrosis previously treated with a JAK inhibitor.

“Momelotinib, an oral JAK1/2 and ACVR1/ALK2 inhibitor, showed clinical activity on [myelofibrosis] symptoms, [red blood cell] transfusion requirements (anemia), and spleen volume in the SIMPLIFY trials,” wrote Ruben A. Mesa, MD, UT Health San Antonio, TX, and colleagues.

The phase 3 MOMENTUM trial aimed to compare momelotinib vs danazol on key symptom, anemia, and spleen volume end points at 24 weeks of treatment.

Patients with primary or post- essential thrombocythemia (ET)/polycythemia vera (PV) myelofibrosis were enrolled. Eligible patients had Dynamic International Prognostic Scoring System (DIPSS) high risk, intermediate-2 risk, or intermediate-1 risk prognosis.

Patients were randomized is a 2:1 ratio to receive momelotinib 200 mg once daily plus placebo or danazol 600 mg once daily plus placebo for 24 weeks, after which patients could receive open-label momelotinib.

The primary end point was total symptom score response rate at week 24. Secondary end points included red blood cell transfusion independence rate, splenic response rate, change from baseline in total symptom score and splenic response rate, and change from baseline in rate of zero transfusions.

Overall, 94 (72%) of 130 patients in the momelotinib arm and 38 (58%) of 65 patients in the danazol arm completed the 24-week randomized treatment phase. Median baseline total symptom score was 28 in the momelotinib arm and 26 in the danazol arm. Median hemoglobin were 8.1 and 7.9 g/dL. Median platelets were 97 and 94 x 10⁹/L, respectively. The baseline transfusion independence rate was 13% with momelotinib and 15% with danazol.

There were 195 (100%) patients who received prior treatment with ruxolitinib and 9 (5%) patients who received prior fedratinib.

The most common grade ≥3 treatment emergent adverse events were thrombocytopenia (momelotinib, 22%; danazol, 12%) and anemia (momelotinib, 8%; danazol, 11%). Treatment–emergent adverse events led to drug discontinuation in 18% of patients receiving momelotinib and 23% of patients receiving danazol.

It was noted that a trend toward improved overall survival up to week 24 was seen with momelotinib vs danazol (hazard ratio, 0.506; P = .0719).

“In symptomatic and anemic [myelofibrosis] pts, [momelotinib] was superior to [danazol] for symptom responses, transfusion requirements, and spleen responses with comparable safety and favorable survival,” concluded Dr Mesa and colleagues.

Source:

Mesa RA, Gerds AT, Vannucchi A, et al. MOMENTUM: Phase 3 randomized study of momelotinib (MMB) versus danazol (DAN) in symptomatic and anemic myelofibrosis (MF) patients previously treated with a JAK inhibitor. Abstract presented at: ASCO Annual Meeting; June 3-7, 2022; Chicago, IL, and virtual. Abstract 7002.