Daratumumab: A Review in Relapsed and/or Refractory Multiple Myeloma.

Intravenous daratumumab (DARZALEX) is a first-in-class human IgG1κ monoclonal antibody against CD38 available for use in patients with relapsed and/or refractory multiple myeloma. In phase I/II and II trials and a pooled analysis of these studies, daratumumab monotherapy induced an overall response (partial response or better) in approximately one-third of patients; responses were rapid, deep and durable. An overall survival (OS) benefit was seen with daratumumab monotherapy, including in patients with a minimal response or stable disease. In phase III trials, daratumumab in combination with either bortezomib plus dexamethasone or lenalidomide plus dexamethasone significantly prolonged progression-free survival and induced deep and durable responses compared with bortezomib plus dexamethasone or lenalidomide plus dexamethasone. An OS benefit with daratumumab triple combination therapy is yet to be demonstrated (as the OS data were not mature at the time of the last analysis). Daratumumab was generally well tolerated when used as monotherapy and had a generally manageable tolerability profile when used in combination therapy. Infusion-related reactions (IRRs) were the most common adverse events; these were predominantly grade 1 or 2 and mostly occurred during the first infusion. The most common grade 3-4 adverse events associated with daratumumab triple combination therapy were thrombocytopenia, neutropenia and anaemia. Although final OS data are awaited, current evidence indicates that daratumumab is a valuable addition to the treatment options currently available for patients with relapsed or refractory multiple myeloma.