Momelotinib in Myelofibrosis Patients With Thrombocytopenia: Post Hoc Analysis From Three Randomized Phase 3 Trials

Abstract

The oral activin A receptor type I, Janus kinase 1 (JAK1), and JAK2 inhibitor momelotinib demonstrated symptom, spleen, and anemia benefits in intermediate- and high-risk myelofibrosis (MF). Post hoc analyses herein evaluated the efficacy and safety of momelotinib in patients with MF and thrombocytopenia (platelet counts <100 × 109/L) from randomized phase 3 studies: MOMENTUM (momelotinib versus danazol; JAK inhibitor experienced); SIMPLIFY-1 (momelotinib versus ruxolitinib; JAK inhibitor naïve); and SIMPLIFY-2 (momelotinib versus best available therapy; JAK inhibitor experienced); these studies were not statistically powered to assess differences in thrombocytopenic subgroups, and these analyses are descriptive. The treatment effect of momelotinib versus ruxolitinib on week 24 response rates (spleen volume reduction ≥35%/Total Symptom Score reduction ≥50%/transfusion independence) was numerically comparable or better in thrombocytopenic patients versus the overall JAK inhibitor naive population; rates were preserved with momelotinib in thrombocytopenic patients but attenuated with ruxolitinib (momelotinib: 27%/28%/67% overall versus 39%/35%/61% in thrombocytopenic group; ruxolitinib: 29%/42%/49% overall versus 0%/22%/39% in thrombocytopenic group, respectively). In contrast to ruxolitinib, momelotinib maintained high dose intensity throughout the treatment. In the JAK inhibitor experienced population, thrombocytopenic patients had the following: (1) numerically higher symptom and transfusion independence response rates with momelotinib than in control arms; and (2) preserved spleen, symptom, and transfusion independence response rates with momelotinib relative to the overall study populations. The safety profile of momelotinib in thrombocytopenic patients was also consistent with the overall study population. In summary, momelotinib represents a safe and effective treatment option for patients with MF and moderate-to-severe thrombocytopenia.

A new mouse model highlights the need for better JAK inhibitors in myeloproliferative neoplasms

“…However, while these inhibitors demonstrate some clinical benefit, they do not adequately reduce the mutant clone fraction. 1 , 2 Consequently, a critical question for the field has been whether the lack of a durable response is attributed to either (i) the inability of current JAK inhibitors to completely block the pathway or (ii) the possibility that mutant clones are not entirely dependent on this activated pathway.…”

Is Treatment for Cytopenic Myelofibrosis Still an Unmet Clinical Need?

“…13 Furthermore, fatigue as a multifactorial and burdensome MF-symptom with significant repercussion on patients' cognitive, physical, and social functioning was shown to be significantly increased in thrombocytopenic MF patients. 14 In a second publication in this HemaSphere issue, Kiladjian et al 15 present data from their post hoc combined analysis of the SIMPLIFY-1, SIMPLIFY-2, and MOMENTUM trials on the efficacy and safety of MMB in patients with thrombocytopenia. All patients with baseline platelet counts of <100 × 10 9 /L were included and defined as the "sub-100 group."…”

“…In a second publication in this HemaSphere issue, Kiladjian et al 15 present data from their post hoc combined analysis of the SIMPLIFY‐1, SIMPLIFY‐2, and MOMENTUM trials on the efficacy and safety of MMB in patients with thrombocytopenia. All patients with baseline platelet counts of <100 × 10 9 /L were included and defined as the “sub‐100 group.” Of note, patients with severe thrombopenia (<50 × 10 9 /L) were not analyzed separately because of low patient numbers but were integrated within the sub‐100 group.…”