Efficacy of Momelotinib in Myelofibrosis Patients: Results From a Multicenter Study

Abstract

Momelotinib, a novel JAK1/2 inhibitor with inhibitory activities on activin A receptor type I, has shown breakthrough clinical efficacy in patients with myelofibrosis (MF) and anemia, a disease-related manifestation of challenging management. In this retrospective real-life multicenter Italian study, we investigated the safety and efficacy of momelotinib in a cohort of 39 consecutive MF patients, regardless of prior therapy. The median duration of treatment was 7 months, and the overall response rate was 56% in transfusion-dependent patients and 46% in the transfusion-independent group. At 24 weeks of treatment, a hemoglobin increase > 1.5 g/dL was observed in 26% of patients, and constitutional symptom improvement was reported in 51% of cases, with a spleen volume reduction > 35% in 28%. Therapy discontinuation occurred in 18% of patients, with only one leukemia progression and three deaths during follow-up. The safety profile was similar to that reported in clinical trials, with most toxicities of grade I-II. In conclusion, our real-life results support the use of momelotinib as an effective and safe therapeutic option for heavily pre-treated, cytopenic MF patients in real-world clinical practice.

Keywords: momelotinib; myelofibrosis; myeloproliferative neoplasms; real‐life.

FIGURE 1

Clinical outcomes of patients receiving momelotinib. (A) Overall survival (OS) and (B) Time on treatment (ToT) of patients with myelofibrosis and anemia treated with momelotinib (N = 39). Patients were also stratified by transfusion dependency (C) or prior administration of another JAK inhibitor, fedratinib (D), and ToT is reported. The number of censored subjects at risk is shown. HR, hazard ratio.

FIGURE 2

Spleen reduction in patients treated with momelotinib. Spleen longitudinal diameter variations are reported for (A) the entire cohort (N = 39) before and after momelotinib administration, or divided based on (B) the presence of JAK2 mutation, prior (C) ruxolitinib or (D) fedratinib treatment, and (E) Dynamic International Prognostic Scoring System (DIPSS) score.

FIGURE 3

Clinical outcomes of the 39 patients with myelofibrosis and anemia enrolled in the study. Swimmer plot with the clinical outcomes of responders (N = 19) and non‐responders (N = 20). Bars represent the follow‐up time for each patient. On the timeline, black bars represent the start of momelotinib treatment until the primary outcome (anemia improvement); green bars represent the time for which patients continued momelotinib on clinical responses, while blue bars represent the time that patients discontinued momelotinib (double vertical bars) and switched to a different drug. Yellow triangles indicate the time of acute myeloid leukemia (AML) progression, and purple crosses indicate that the patient died.