Objective To review the clinical pharmacology, efficacy and safety of daratumumab and elotuzumab for the treatment of relapsed refractory multiple myeloma. Data sources A literature search of Medline, PubMed, the U.S. 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 multiple myeloma were identified. Data synthesis Daratumumab (anti-CD38) and elotuzumab (anti-CS1) have been recently FDA approved for the treatment of relapsed refractory multiple myeloma (RRMM) after showing extraordinary efficacy in trials Elotuzumab approval based on phase III data whereas daratumumab was approved based on phase I/II trials. Daratumumab has demonstrated significant single agent activity with ORR of 36% in patients with median of 4 prior lines of therapy. On the other hand, elotuzumab has no single agent activity. But, the efficacy of both these antibodies in combination with lenalidomide and dexamethasone in RRMM showed an overall response rate (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.
【저자키워드】 Treatment, Immunotherapy, monoclonal antibodies, Multiple myeloma, daratumumab, refractory, elotuzumab, Relapsed,