Longitudinal Safety of Luspatercept in the Treatment of Anemia in Patients with Myelofibrosis: Results from the ACE-536-MF-001 Study

Introduction Luspatercept (LUSPA) is approved for the treatment of anemia in some adults with β-thalassemia or myelodysplastic syndrome who require red blood cell transfusion and has a well characterized safety profile for these indications. The primary readout from the phase 2 ACE-536-MF-001 study (NCT03194542) demonstrated manageable safety and promising efficacy of LUSPA for treatment of myelofibrosis (MF)-related anemia with 19.0%-31.6% of patients (pts) achieving transfusion independence (defined as 84 consecutive days transfusion free), and 18.2%-21.4% of non-transfusion-dependent (NTD) pts achieving anemia response (defined as 84 consecutive days ≥ 1.5 g/dL hemoglobin increase from baseline without transfusion) in the entire treatment period (Gerds ASCO 2023 7016). To characterize further the safety profile of LUSPA in MF and provide data on adverse event (AE) management, we present a detailed longitudinal safety analysis of the MF-001 study. Methods Pts were enrolled into 4 cohorts based on transfusion dependence (TD) and stable ruxolitinib (RUX) treatment - cohort 1: NTD, no RUX; cohort 2: TD, no RUX; cohort 3A: NTD, RUX; cohort 3B: TD, RUX. All pts received LUSPA 1.0 mg/kg subcutaneously with titration up to 1.75 mg/kg in 21-day cycles; the starting dose was 1.33 mg/kg in the cohort 3B expansion group. Response was assessed at day 169 (24 weeks), with treatment extended for pts showing clinical benefit. The primary endpoint was anemia response; AEs alongside LUSPA and RUX dosing were also assessed. On dosing days, seated blood pressure was assessed prior to LUSPA administration. In the case of ≥ grade 3 hypertension (systolic ≥ 160 mmHg, diastolic ≥ 100 mmHg), dosing was delayed until hypertension had resolved to ≤ grade 1 or baseline, followed by dose reduction by 1 dose level. If ≥ 2 dose reductions were implemented due to any suspected treatment-related AE (TRAE), LUSPA was discontinued. Results In the safety population (N = 95; cohort 1, n = 22; cohort 2, n = 14; cohort 3A, n = 21; cohort 3B, n = 38), the most frequently used prior medications for anemia treatment were erythropoiesis-stimulating agents (23.2%, most frequently epoetin alfa [14.7%]), followed by danazol (11.6%), lenalidomide (2.1%), and thalidomide (1.1%). Prior history of hypertension was recorded in 50.5% of pts. Median follow-up duration was 546 days. A total of 47.4% of pts had ≥ 1 TRAE; the most common were hypertension (17.9%), bone pain (7.4%), and diarrhea (6.3%). Incid