By: Aaron Gerds, Claire Harrison, Jean-Jacques Kiladjian, Ruben Mesa, Alessandro Vannucchi, Rami Komrokji, Prithviaj Bose, Marina Kremyanskaya, Adam Mead, Jason Gotlib, Shelonitda Rose, Fabian Sanabria, Niloufar Marsousi, Ana Giuseppi, Huijing Jiang, Jeanne Palmer , Kelly McCaul, Vincent Ribrag, Francesco Passamonti
Abstract:
The ACE-536-MF-001 trial enrolled patients with myelofibrosis (n = 95) into 4 cohorts: patients in
cohorts 1 and 3A were non-transfusion dependent (NTD) and had anemia; patients in cohorts 2 and 3B
were transfusion dependent (TD); patients in cohort 3A/3B had stable ruxolitinib treatment prior to
and during the study. All patients received luspatercept (1.0-1.75 mg/kg, 21-day cycles). Treatment
was extended if clinical benefit was observed at day 169. The primary endpoint was anemia response
rate (NTD, {greater than or equal to}1.5 g/dL hemoglobin increase from baseline; TD, transfusionindependence) over any 12-week period during the primary treatment period (weeks 1-24). Overall, 14% of patients in cohorts 1 and 3A, 10% in cohort 2, and 26% in cohort 3B met the primary
endpoint. In cohorts 1 and 3A (NTD), 27% and 50% of patients respectively had mean hemoglobin
increase {greater than or equal to}1.5 g/dL from baseline. Among TD patients, ~50% had {greater
than or equal to}50% reduction in transfusion burden. Reduction in total symptom score was observed
in all cohorts, with the greatest response rate seen in cohort 3A. Overall, 94% of patients had
{greater than or equal to}1 adverse event (AE); 47% had {greater than or equal to}1 treatmentrelated AE (TRAE; 11% grade {greater than or equal to}3), most frequently hypertension (18%),
managed with medical intervention. One patient had a serious TRAE leading to luspatercept
discontinuation. Nine patients died on treatment (unrelated to study drug). In most patients,
ruxolitinib dose and spleen size remained stable. In patients with myelofibrosis, luspatercept
improved anemia and transfusion burden across cohorts.