Sotatercept in patients with osteolytic lesions of multiple myeloma

• DOI: 10.1111/bjh.12835
• Publication Date: 2014-03-21T06:44:41Z
• Authors: Kudrat M. Abdulka...; Galina N. Salogub; Nuriet K. Khuazheva; Matthew L. Sherman; Abderrahmane Laadem; Rachel Barger; Robert Knight; Shankar Srinivasan; Evangelos Terpos
• Keywords: Adult; Male; Haematological Malignancy; Recombinant Fusion Proteins; Antineoplastic Agents; Osteolysis; Middle Aged; 3. Good health; 03 medical and health sciences; Treatment Outcome; 0302 clinical medicine; Bone Density; Osteogenesis; Antineoplastic Combined Chemotherapy Protocols; Humans; Immunologic Factors; Female; Multiple Myeloma; Biomarkers; Aged; Neoplasm Staging

SummaryThis phaseIIa study evaluated the safety and tolerability of sotatercept, and its effects on bone metabolism and haematopoiesis in newly diagnosed and relapsed multiple myeloma (MM) patients. Patients were randomized (4:1) to receive four 28‐d cycles of sotatercept (0·1, 0·3, or 0·5 mg/kg) or placebo. Patients also received six cycles of combination oral melphalan, prednisolone, and thalidomide (MPT). Thirty patients were enrolled; six received placebo and 24 received sotatercept. Overall, 25% of patients received all four sotatercept doses; 71% of sotatercept‐treated patients had ≥1 dose interruption mainly due to increases in haemoglobin levels. Grade ≥3 adverse events (AEs) were reported in 17% of patients receiving placebo and 58% receiving sotatercept. Grade 4AEs in sotatercept‐treated patients were neutropenia, granulocytopenia, and atrial fibrillation (one patient each). In patients without bisphosphonate use, anabolic improvements in bone mineral density and in bone formation relative to placebo occurred, whereas bone resorption was minimally affected. Increases in haemoglobin levels,versusbaseline, and the duration of the increases, were higher in the sotatercept‐treated patients, with a trend suggesting a dose‐related effect. Multiple doses of sotatercept plusMPTappear to be safe and generally well‐tolerated inMMpatients.