CLINICAL NEWS
Luspatercept Leads to Increased Hemoglobin
Levels, Transfusion Independence in MDS Patients
Treatment with luspatercept, an investigational fusion
protein for the treatment of anemias with ineffective red
blood cell (RBC) production, was associated with increased hemoglobin counts and greater rates of transfusion-independence in patients with lower-risk myelodysplastic syndromes (MDS), according to preliminary data
from the phase II PACE-MDS extension study.
“MDS patients have increase Smad2/3 signaling in
the bone marrow, leading to ineffective erythropoiesis,”
lead author Aristoteles Giagounidis, MD, PhD, head of
the Department of Oncology, Hematology, and Palliative Care at Marien Hospital in Düsseldorf, Germany,
explained in his presentation during the 2015 ASH
Annual Meeting in Orlando, Florida. “Luspatercept
inhibits Smad2/3 signaling and promotes late-stage erythroid differentiation, thereby correcting the ineffective
erythropoiesis.” Luspatercept contains a modified activin
receptor B, fused to a human IgG Fc domain. The activin
receptor is responsible for blockade of TGF-b superfamily
ligands, which in turn inhibits Smad2/3 signaling.
Dr. Giagounidis reported results from the 24-month
extension of the phase II, multi-center, open-label
PACE-MDS study, which evaluated the longer-term
effects of luspatercept on anemia in 32 patients with
lower-risk MDS (IPSS classification of low/int-1). In the
PACE-MDS base study, patients were eligible for inclusion if they were ≥18 years old, had anemia with high
or low transfusion burden and hemoglobin <10.0 g/dL,
and were non-responsive or refractory to erythropoiesis-stimulating