Evolving Role of Daratumumab: From Backbencher to Frontline Agent

Approval of daratumumab (DARA), an IgGk1 monoclonal antibody targeting CD38, for the treatment of relapsed/refractory multiple myeloma as monotherapy in November 2015 expanded the therapeutic armamentarium for multiple myeloma. Widespread tissue expression of CD38 combined with potent immunomodulatory activity provides a rationale for the expanding use of DARA and potential new marketing authorizations. Novel combinations of DARA have been built on the basis of preclinical data of synergy and overcoming DARA resistance. Newer delivery strategies have led to the administration of DARA in community settings. Despite a remarkable tolerability profile in elderly myeloma patients, DARA use increases the risk of infections, particularly virus reactivation, requiring close monitoring and/or prophylaxis. We aim to provide an in-depth review of the mechanisms of action, resistance, and synergies of DARA and to highlight its current clinical uses and potential future perspectives. Laboratory issues with the use of DARA and their mitigation strategies are also discussed.