MOMENTUM trial: Updates from ASH 2022

The pivotal phase III MOMENTUM study (NCT04173494) was designed to confirm the differentiated clinical benefits of momelotinib versus danazol in anemic patients with symptomatic myelofibrosis (MF) previously treated with a JAK inhibitor.¹

The MPN Hub previously reported on updates from the MOMENTUM trial presented at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting, where the study design and 24-week outcomes can be reviewed. Of note, ~50% of patients were transfusion dependent at baseline, with a further ∼35% of patients receiving some transfusions.¹

Here, we summarize updated efficacy and safety data presented by Aaron Gerds at the 64th American Society of Hematology (ASH) Annual Meeting and Exposition following the completion of all patients’ 48-week assessments, including data specific to patients with thrombocytopenia.¹

TSS, TI, and spleen responses at Week 48

The 24-week total symptom score (TSS), transfusion independence (TI), and spleen responses were sustained at Week 48 (Table 1).

Table 1. TSS, TI, and spleen responses at Week 48

SRR35, splenic response rate with a 35% reduction; TI, transfusion independence; TSS, total symptom score. *Adapted from Gerds.1
Response, %	Momelotinib continued	Danazol crossover to momelotinib
TSS
At Week 24	25	9
Maintained at Week 48	97	100
TI
At Week 24	31	20
Maintained at Week 48	90	77
SRR35
At Week 24	23	3
Maintained at Week 28	100	100

Of non-responders at Week 24, 29% of patients treated with danazol who switched to momelotinib were new responders by Week 48, as were 20% of momelotinib non-responders. These results indicate that a longer duration of therapy may be beneficial for patients treated with momelotinib.

Overall survival and leukemia-free survival at Week 48

Overall survival (OS) and leukemia-free survival curves converged for patients who continued momelotinib treatment or switched from danazol to momelotinib at Week 24. For patients who remained on momelotinib, OS was significantly improved at Week 48 for those who achieved a TI response at Week 24.

Efficacy results in patients with thrombocytopenia (platelets <100 × 10⁹/L) were consistent with the general study population. In subsets of patients with thrombocytopenia, improved OS benefit was seen in patients with baseline platelets (<50 × 10⁹/L) for momelotinib versus danazol. However, study numbers were small, warranting further investigation.

Safety at Week 48

Grade ≥3 and serious adverse event rates at 48 weeks were comparable between the two arms (Table 2).

Table 2. Grade ≥3 and serious adverse event rates at 48 weeks*

AE, adverse event; SAE, serious adverse event; TEAE, treatment-emergent adverse event. *Adapted from Gerds.1
TEAE, %	Momelotinib continued	Danazol crossover to momelotinib
Grade ≥3 AEs	49.5	46.3
SAEs	31.2	29.3

• No new safety signals were detected.
• Rates of peripheral neuropathy were very low in both arms (2.2% for momelotinib continuation and 2.4% for danazol to momelotinib).

• Safety in patients with thrombocytopenia (platelets <100 × 10⁹/L) were consistent with the general study population.

Conclusion

In this updated analysis, momelotinib maintained 24-week symptom, TI, and spleen responses at Week 48 in symptomatic and anemic patients with MF, with favorable survival and safety outcomes. The study reports sustained TSS response at Week 48 and new TSS responses beyond Week 24. Efficacy and safety results in patients with thrombocytopenia were consistent with those of the general study population. These findings indicate that momelotinib may address a critical unmet need in patients with MF and anemia, including those with severe thrombocytopenia.