Drug enables transfusion independence in lower-risk MDS
COPENHAGEN—Results from a pair of phase 2 trials suggest luspatercept can produce erythroid responses and enable transfusion independence in patients with lower-risk myelodysplastic syndromes (MDS).
In a 3-month base study, 51% of patients treated with luspatercept had an erythroid response, and 35% achieved transfusion independence.
In an ongoing extension study, 81% of luspatercept-treated patients have had an erythroid response, and 50% have achieved transfusion independence.
The majority of adverse events in both trials were grade 1 and 2.
Uwe Platzbecker, MD, of the University Hospital in Dresden, Germany, presented these results at the 21st Congress of the European Hematology Association (abstract S131*). The studies were sponsored by Acceleron Pharma, Inc.
Luspatercept (formerly ACE-536) is a modified activin receptor type IIB fusion protein that increases red blood cell (RBC) levels by targeting molecules in the TGF-β superfamily. Acceleron and Celgene are developing luspatercept to treat anemia in patients with rare blood disorders.
The phase 2 base study was a dose-escalation trial in which MDS patients received luspatercept for 3 months. In the ongoing extension study, patients from the base study are receiving luspatercept for an additional 24 months.
In both studies, patients with high transfusion burden (≥4 RBC units/8 weeks) and those with low transfusion burden (<4 RBC units/8 weeks) received luspatercept once every 3 weeks.
Base study
This study included 58 patients with a median age of 71.5 (range, 27-90). Their median time since diagnosis was 2.4 years (range, 0-14). Seventeen percent of patients had prior lenalidomide treatment, and 66% had previously received erythropoiesis-stimulating agents (ESAs).
In patients with low transfusion burden (n=19), the median hemoglobin at baseline was 8.7 g/dL (range, 6.4-10.1). In patients with high transfusion burden (n=39), the median number of RBC units transfused per 8 weeks was 6 (range, 4-18).
Patients received luspatercept subcutaneously every 3 weeks for up to 5 doses. The study included 7 dose-escalation cohorts (n=27, 0.125 to 1.75 mg/kg) and an expansion cohort (n=31, 1.0 to 1.75 mg/kg).
The primary outcome measure was the proportion of patients who had an erythroid response. In non-transfusion-dependent patients, an erythroid response was defined as a hemoglobin increase of at least 1.5 g/dL from baseline for at least 14 days.
In transfusion-dependent patients, an erythroid response was defined as a reduction of at least 4 RBC units transfused or a reduction of at least 50% of RBC units transfused compared to pretreatment.
Fifty-one percent (25/49) of patients treated at the higher dose levels had an erythroid response. And 35% (14/40) of transfused patients treated at the higher dose levels were transfusion independent for at least 8 weeks.
Extension study
This study includes 32 patients with a median age of 71.5 (range, 29-90). Their median time since diagnosis was 2.9 years (range, 0-14). Nineteen percent of patients had prior lenalidomide treatment, and 59% had previously received ESAs.
In patients with low transfusion burden (n=13), the median hemoglobin at baseline was 8.5 g/dL (range, 6.4-10.1). In patients with high transfusion burden (n=19), the median number of RBC units transfused per 8 weeks was 6 (range, 4-14).
In this ongoing study, patients are receiving luspatercept (1.0 to 1.75 mg/kg) subcutaneously every 3 weeks for an additional 24 months.
At last follow-up (March 4, 2016), 81% (26/32) of patients had an erythroid response. And 50% (11/22) of patients who were transfused prior to study initiation achieved transfusion independence for at least 8 weeks (range, 9-80+ weeks).
Dr Platzbecker noted that, in both studies, erythroid responses were observed whether or not patients previously received ESAs and regardless of patients’ baseline erythropoietin levels.
