Immunotherapy: A New Approach to Treating Multiple Myeloma with Daratumumab and Elotuzumab

Objective: To review the clinical pharmacology, efficacy, and safety of daratumumab and elotuzumab for the treatment of relapsed refractory multiple myeloma (RRMM). Data Sources: A literature search of MEDLINE, PubMed, the US National Institutes of Health Clinicaltrials. gov, the Food and Drug administration, and relevant meeting abstracts was conducted using the terms daratumumab, elotuzumab, multiple myeloma, anti-CD38, HuMax-CD38, HuLuc63, SLAMF7, and anti-CS1. Study Selection/Data Extraction: Human and animal studies describing the pharmacology, pharmacokinetics, efficacy, and safety of daratumumab and elotuzumab for MM were identified. Data Synthesis: Daratumumab (anti-CD38) and elotuzumab (anti-CS1) have been recently FDA approved for the treatment of RRMM after showing efficacy in clinical trials. Elotuzumab approval was based on phase III data, and daratumumab gained accelerated approval based on phase I/II trials. Daratumumab has demonstrated significant single-agent activity, with an overall response rate (ORR) of 36% in patients with a median of 4 prior lines of therapy. Elotuzumab has not been shown to have single-agent activity. But the efficacy of both these antibodies in combination with lenalidomide and dexamethasone in RRMM showed an ORR exceeding 80%. Tolerability of elotuzumab and daratumumab seems to be acceptable, with the most common adverse event being infusion reactions. Conclusion: Daratumumab and elotuzumab have shown encouraging results in RRMM that led to their FDA approval. Both are well tolerated with minimal toxicities. Phase III clinical trials will define optimal combination and place in therapy of daratumumab and elotuzumab.