Transfusion Independence is Associated with Improved Overall Survival in Myelofibrosis Patients Receiving Momelotinib

Background Momelotinib (MMB) is a potent JAK1, JAK2, and ACVR1/ALK2 inhibitor with clinical activity against the hallmark features of myelofibrosis (MF), namely anemia, constitutional symptoms, and splenomegaly, as demonstrated in the Phase 3 SIMPLIFY-1 and -2 clinical trials (S1, S2). S1 enrolled JAKi-naive patients (n = 432) double-blind randomized 1:1 to MMB or ruxolitinib (RUX). S2 enrolled patients with hematological toxicity during prior RUX therapy (n = 156) randomized 2:1 to open-label MMB or best available therapy (BAT; RUX in 88% of patients). In both trials, following 24 weeks of randomized treatment, patients could continue MMB, and those randomized to RUX/BAT could cross-over to MMB for extended treatment. Previously published data from the SIMPLIFY studies demonstrate robust overall survival (OS) for MMB-treated patients in S1 and S2 (median not reached and 34.3 months, respectively) with a maximum follow-up of approximately 5 years and median of 2.9 years in S1 and 2.3 years in S2. Objectives and Methods OS data for patients receiving MMB in S1 and S2 were analyzed for subgroups defined by week 24 (W24) transfusion-independent (TI) responders vs non-responders and also other efficacy endpoints. Survival was estimated using KM analysis with descriptive log-rank tests for comparison applied (all p-values are descriptive). Results As previously reported, W24 TI rates were higher in the MMB arms of S1 (67% vs 49%) and S2 (43% vs 21%). In S1, W24 TI responders in the MMB group show an OS advantage compared to MMB TI non-responders, with median OS not reached and 3-year survival of 80% (HR = 0.30; p Conclusions These new analyses suggest JAKi-naive patients receiving MMB who maintain or achieve TI at W24 have favorable OS compared to MMB TI non-responders, with a similar trend observed in previously RUX-exposed patients. The findings that TI may predict improved OS in MF suggest that the goal of achieving or maintaining TI could become an important driver of treatment decisions.