Department of Hematology, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, India.
Department of Haematology, Oxford University Hospitals, NHS Foundation Trust, Oxford, UK; Department of Haematology, NIHR BRC Blood Theme, Oxford, UK; Department of Haematology, Oxford Myeloma Centre for Translational Research, Oxford, UK.
Clin Lymphoma Myeloma Leuk. 2020 Sep;20(9):572-587. doi: 10.1016/j.clml.2020.03.010. Epub 2020 Apr 2.
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.
达雷妥尤单抗（DARA）于 2015 年 11 月获批，作为单药用于治疗复发/难治性多发性骨髓瘤，这为多发性骨髓瘤的治疗提供了更多选择。CD38 在广泛组织中表达，同时具有强大的免疫调节活性，为 DARA 的广泛应用和潜在的新适应证提供了理论依据。新型 DARA 联合方案基于协同作用和克服 DARA 耐药性的临床前数据。新的给药策略使 DARA 可在社区环境中使用。尽管在老年骨髓瘤患者中具有显著的耐受性，但 DARA 的使用会增加感染的风险，特别是病毒再激活，需要密切监测和/或预防。我们旨在深入探讨 DARA 的作用机制、耐药性和协同作用，并强调其目前的临床应用和潜在的未来前景。本文还讨论了 DARA 应用中的实验室问题及其缓解策略。
