Momelotinib Improves OS in Patients With Myelofibrosis and Low Platelet Counts

Momelotinib induced superior 24-week overall survival (OS) rates compared with danazol in thrombocytopenic, symptomatic, and anemic patients with myelofibrosis, according to data from the phase 3 MOMENTUM trial (NCT04173494) presented at the 2022 SOHO Annual Meeting.¹

Investigators evaluated the safety and efficacy of the JAK inhibitor in comparison with danazol in patients with myelofibrosis who had baseline platelet counts of ≤150 x 10⁹/L, <100 x 10⁹/L, and <50 x 10⁹/L. Notably, investigators observed responses even in patients with platelet counts as low as 25 x 10⁹/L. At 24 weeks, the OS rate for patients with a platelet count <100 x 10⁹/L was 86.2% with momelotinib and 82.1% with danazol. For patients with a platelet count <50 x 10⁹/L, the OS rate was 94.4% vs 59.8%, respectively.

Investigators in MOMENTUM enrolled patients with symptomatic (total symptom score [TSS] ≥10) and anemic (hemoglobin <10 g/dL) myelofibrosis who previously received a JAK inhibitor. A total of 195 patients with taper and washout over at least 3 weeks and dosed with a JAK inhibitor therapy were randomly assigned to 200 mg momelotinib or 600 mg danazol per day.

Early crossover was permitted to patients on the danazol arm who had confirmed disease progression; those patients then went on to receive open-label 200 mg daily dose of momelotinib.

Participants were stratified by TSS, palpable spleen length, number of red blood cell (RBC) units transfused in the 8 weeks before randomization, and study site. Investigators conducted the study during the COVID-19 quarantine.

The primary end point of the trial was TSS response rate (≥50% reduction from baseline; TSS50) at week 24. Key secondary end points included transfusion independence response (TIR) and ≥35% splenic volume reduction from baseline (SVR35).

In the <100 x 10⁹/L group, the mean age was 70.0 in the experimental arm (n = 66) vs 70.6 in the danazol arm (n = 34). Forty (60.6%) of patients in the momelotinib group were male compared with 23 (67.6%) in the control arm. The majority of patients in both arms were white (80.3% vs 73.5%, respectively).

The mean TSS was 27.7 at baseline in the experimental arm vs 24.9 in the control arm. Mean prior JAK inhibitor duration was 145.6 weeks (standard deviation [SD], 127.5) and 137.8 weeks (SD, 119.4), respectively.

In the <50 x 10⁹/L group, the mean age was 72.6 in the experimental arm (n = 18) vs 70.2 in the danazol arm (n = 13). Eleven (61.1%) of patients in the momelotinib group were male compared with 7 (53.8%) in the control arm. The majority of patients in both arms were white (83.3% vs 53.8%, respectively).

The mean TSS was 29.4 at baseline in the experimental arm vs 27.2 in the control arm. Mean prior JAK inhibitor duration was 150.7 weeks (SD, 144.6) and 110.6 weeks (SD, 87.8), respectively.

In the <100 x 10⁹/L group, TSS50 (29% vs 15%), TIR (27% vs 21%), and SVR35 (20% vs 6%) all favored the experimental agent. Similarly, outcomes in the <50 x 109/L group, TSS50 (22% vs 8%), TIR (17% vs 15%), and SVR35 (22% vs 0%) also favored momelotinib.

In the <100 x 10⁹/L group, 60.6% of patients in the experimental arm experienced grade 3 or greater treatment-emergent adverse effects (TEAEs) compared with 61.8% in the danazol arm. Twenty-eight patients (42.4%) in the experimental arm experienced serious TEAEs compared with 11 (32.4%) in the control arm.

Twelve (18.2%) patients required momelotinib discontinuation due to TEAEs. Twenty-six (39.4%) required dose reduction or interruption. Those rates were 14.7% and 26.5%, respectively, in the control arm. The most common grade 3 or higher TEAEs in the experimental group were thrombocytopenia (33.3%) and anemia (9.1%), compared with 20.6% and 11.8%, respectively, in the control group.

In the <50 x 10⁹/L group, 55.6% of patients in the experimental arm experienced grade 3 or higher TEAEs compared with 69.2% in the danazol arm. Eight patients (44.4%) in the experimental arm experienced serious TEAEs vs 6 patients (46.2%) in the control arm.

Two patients (11.1%) required momelotinib discontinuation due to TEAEs. Eight patients (44.4%) required dose reduction or interruption. Those findings were 23.1% and 15.4%, respectively, in the control arm. The most common grade 3 or higher TEAEs in the experimental group were thrombocytopenia (44.4%), anemia (22.2%), and dyspnea (11.1%) compared with 15.4%, 23.1%, and 0%, respectively, in the control group.

In previously reported findings from the intention-to-treat population presented at the 2022 EHA Congress, TSS response rate at week 24 with momelotinib (n = 130) was 24.6% (95% CI, 17.49%-32.94%) vs 9.2% (95% CI, 3.46%-19.02%) with danazol (n = 65; P = .0095). Patients needed to achieve at least a 50% reduction in TSS compared with baseline to establish superiority.²

Momelotinib was also found to be superior to danazol in terms of spleen response rate at week 24, at both the 25% and 35% reduction thresholds. Specifically, 40.0% (95% CI, 31.51%-48.95%) of those who received momelotinib achieved at least a 25% SVR vs 6.2% (95% CI, 1.70%-15.01%) of those who were given danazol (P < .0001). Moreover, 23.1% (95% CI, 16.14%-31.28%) of those in the momelotinib arm achieved at least a 35% SVR vs 3.1% (95% CI, 0.37%-10.68%) in the danazol arm (P = .0006).

In August 2022, the FDA accepted a new drug application for momelotinib for the treatment of patients with myelofibrosis.³

References

1. 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: the 2022 SOHO Annual Meeting; September 28-October 1, 2022; Houston, TX. Abstract MPN-483.
2. Verstovsek S, Vannucchi A, Gerds AT, 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. Presented at: 2022 EHA Congress; June 9-12, 2022; Vienna, Austria. Abstract S195.
3. US FDA accepts new drug application for GSK’s momelotinib for the treatment of myelofibrosis. News release. GSK. August 17, 2022. Accessed September 30, 2022. https://bit.ly/3K4Azcq