Komrokji R, et al. - Researchers here sought to establish a safe and effective dose of sotatercept for the treatment of anaemia in patients with lower-risk myelodysplastic syndromes. Sotatercept was well tolerated and effective for the treatment anemia among the patients in whom previous erythropoiesis-stimulating agent (ESA) treatment had failed. For these patients who have few available treatment options, treatment with sotatercept could be valuable.

Methods

• Researchers performed an open-label, multicentre, dose-ranging, phase 2 trial at 11 treatment centres in the USA and France.
• Eligible patients were those who fulfilled the following criteria: aged 18 years or older, had International Prognostic Scoring System-defined low-risk or intermediate-1-risk myelodysplastic syndromes, had anaemia requiring red blood cell (RBC) transfusions, and were ineligible for, or refractory to, ESAs.
• If patients had chromosome 5q deletion myelodysplastic syndromes without documented failure of lenalidomide, they were not eligible.
• They randomly assigned the patients to receive either 0·1 or 0·3 mg/kg sotatercept subcutaneously, using a permuted-block method with stratification for serum erythropoietin concentration and transfusion burden.
• In a non-randomised fashion, they assigned the patients to 0·5, 1·0, and 2·0 mg/kg groups.
• The proportion of patients who achieved haematological improvement–erythroid (HI-E), according to International Working Group 2006 criteria was assessed as the primary efficacy endpoint .
• In the intention-to-treat population, they performed efficacy and safety analyses.

Results

• Researchers enrolled 74 patients in this study from Dec 5, 2012, to July 22, 2015(seven to receive 0·1 mg/kg sotatercept, six to 0·3 mg/kg, 21 to 0·5 mg/kg, 35 to 1·0 mg/kg, and five to 2·0 mg/kg).
• In this study, 36 (49%; 95% CI 38–60) of 74 patients achieved HI-E; 29 (47%; 95% CI 35–59) of 62 patients with a high transfusion burden achieved HI-E (RBC-transfusion reduction from baseline of 4 or more units for at least 56 days), and 7 (58%; 95% CI 32–81) of 12 patients with a low transfusion burden achieved HI-E (haemoglobin increase of 1·5 g/dL or more sustained for at least 56 days in the absence of transfusions).
• Adverse events, most commonly reported were fatigue in 19 (26%) of 74 patients and peripheral oedema in 18 (24%) of 74 patients.
• In 25 (34%) of 74 patients, researchers reported grade 3–4 treatment-emergent adverse events (TEAEs); grade 3–4 TEAEs that were considered to be treatment related were observed in 4 (5%) patients.
• Lipase increase and anaemia were the most common grade 3–4 TEAEs, each of these occurred in three (4%) of 74 patients.
• At least 1 serious TEAE was evident in 17 (23%) of 74 patients, and there was 1 patient who died from a treatment-emergent subdural haematoma due to a fall.