title: Sotatercept in patients with osteolytic lesions of multiple myeloma.
abstract: This phase IIa 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 4 AEs 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, versus baseline, 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 plus MPT appear to be safe and generally well-tolerated in MM patients.
authors.affiliation: Russian Research Institute of Haematology and Blood Transfusion, St Petersburg, Russia.
authors.forename: Kudrat M
authors.initials: KM
authors.lastname: Abdulkadyrov
authors.forename: Galina N
authors.initials: GN
authors.lastname: Salogub
authors.forename: Nuriet K
authors.initials: NK
authors.lastname: Khuazheva
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Sherman
authors.forename: Abderrahmane
authors.initials: A
authors.lastname: Laadem
authors.forename: Rachel
authors.initials: R
authors.lastname: Barger
authors.forename: Robert
authors.initials: R
authors.lastname: Knight
authors.forename: Shankar
authors.initials: S
authors.lastname: Srinivasan
authors.forename: Evangelos
authors.initials: E
authors.lastname: Terpos
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D015415:Biomarkers; D015519:Bone Density; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000150:complications / Q000188:drug therapy* / Q000473:pathology*; D009367:Neoplasm Staging; D010012:Osteogenesis; D010014:Osteolysis / Q000209:etiology / Q000473:pathology*; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers; D007155:Immunologic Factors; D011993:Recombinant Fusion Proteins; C542017:sotatercept
keywords: anaemia; bone disease; haematopoiesis; multiple myeloma; sotatercept