Phase I safety data of lenalidomide, bortezomib, dexamethasone, and elotuzumab as induction therapy for newly diagnosed symptomatic multiple myeloma: SWOG S1211

Novel drugs including immunomodulatory agents and proteasome inhibitors have improved outcomes in plasma cell dyscrasias, but high-risk multiple myeloma (HRMM) retains a poor prognosis and remains a therapeutic challenge. Even with aggressive Total Therapy approaches, poor genomic risk patients have a 2-year event-free survival of ~50%. 1 An intergroup, randomized trial was designed to evaluate the efficacy of adding elotuzumab (Elo) into the front line for HRMM, comparing lenalidomide, bortezomib and dexamethasone (RVd) with or without Elo. This agent is a humanized monoclonal antibody to SLAMF7, a cell surface glycoprotein on myeloma cells but with limited expression on normal cells, 2 and early clinical studies of Elo has shown promise. In a phase I of Elo/bortezomib, the overall response rate (ORR), including partial response (PR) or better, was 48%. 3 In Phase Ib 4 and II 5 studies of Elo/Rd, the ORR was 82% and 92%, respectively, for patients treated with Elo at 10 mg/kg. For all Elo studies, adverse events (AEs) were primarily infusion related and manageable using adequate premedication. Though limited, the data available suggest these Elo-based combinations have comparable response rates in high-risk and standard-risk relapsed and/or refractory patients, providing a rationale for its incorporation into front-line HRMM therapy.