MPN-106: Improved Transfusion Independence Rates for Momelotinib vs Ruxolitinib in Anemic JAKi-Naïve Myelofibrosis Patients are Independent of Baseline Platelet or Transfusion Status

Abstract

Background: Momelotinib (MMB) is a JAK1, JAK2, and ACVR1/ALK2 inhibitor with clinical activity against the hallmark features of myelofibrosis (MF), namely anemia, constitutional symptoms, and splenomegaly, across the continuum of JAK inhibitor (JAKi)-naive or previously JAKi-treated patients. Inhibition of ACVR1/ALK2 reduces hepcidin; elevated levels of hepcidin cause an iron-restricted anemia of inflammation, shortening overall survival (OS) in patients with MF. Previously reported data from the SIMPLIFY-1 (S1) Phase 3 trial in JAKi-naive patients with MF (n=432) double-blind randomized 1:1 to MMB or ruxolitinib (RUX) show the overall week 24 (W24) transfusion independence (TI) rate was 67% for MMB vs 49% for RUX. A robust median OS of 53 months was shown in patients originally randomized to RUX, followed by MMB and Not Reached (NR) in patients randomized to MMB. Objectives and Methods: Given the previously reported positive impact of TI on OS in patients randomized to MMB, we expanded the retrospective platelet (PLT) subset analysis to explore the W24 TI response rates for MMB and RUX randomized patients in S1 by baseline (BL) hemoglobin (Hgb) and PLT levels and transfusion status. Results: Treatment with MMB resulted in higher TI rates vs RUX in all patient subsets with BL Hgb ≤ 14 g/dL and all subsets defined by BL PLTs and BL transfusion status. Patient subsets with BL Hgb ≤ 14 g/dL account for 93% of patients in S1, representing a population where the majority have some degree of anemia. Conclusions: The previously reported finding that TI may predict improved OS in MF suggests that the goal of achieving or maintaining TI could become an important driver of treatment decisions. The data presented here support the breadth of W24 TI benefits for patients receiving MMB, irrespective of the degree of anemia, PLT count, or transfusion status at baseline. Taken together, these data further support the potential benefit of MMB’s ACVR1/ALK2 inhibitory activity, in addition to JAK1 and JAK2 inhibition, leading to improved TI rates and OS.