多发性骨髓瘤(MM)是一种血液恶性肿瘤，定义为转化浆细胞的克隆增殖。尽管MM治疗范式取得了巨大进展，但对于大多数患者来说，治愈仍然是个难题。虽然很大一部分患者能够获得长期疾病控制，但肿瘤耐药性的产生会导致疾病复发，尤其是对于三重类耐药MM（定义为对免疫调节剂、蛋白酶体抑制剂和单克隆抗体的抗药性患者）。这类患者需要有效的治疗方案。嵌合抗原受体（CAR）T细胞疗法是一种新方法，在治疗复发性、难治性MM(RRMM)中表现出了很好的疗效。这些基因修饰的细胞疗法已经在其他B细胞恶性肿瘤中证明了深刻和持久的缓解，目前的努力是在RRMM患者中实现类似的结果。早期研究表明，CAR T细胞疗法在RRMM中有显著的响应率；然而，在骨髓瘤中使用CAR T细胞疗法的持久缓解尚未被实现。在本综述中，作者描述了在MM中开发CAR T细胞疗法的过程、显著临床试验的结果、CAR T细胞疗法的毒副作用和局限性，以及克服CAR T细胞治疗挑战的策略，希望实现多发性骨髓瘤的治愈。© 2023年作者。 由Wiley Periodicals LLC代表美国癌症协会出版的《癌症临床医学杂志》。

Multiple myeloma (MM) is a hematologic malignancy defined by the clonal proliferation of transformed plasma cells. Despite tremendous advances in the treatment paradigm of MM, a cure remains elusive for most patients. Although long-term disease control can be achieved in a very large number of patients, the acquisition of tumor resistance leads to disease relapse, especially in patients with triple-class refractory MM (defined as resistance to immunomodulatory agents, proteosome inhibitors, and monoclonal antibodies). There is an unmet need for effective treatment options in these patients. Chimeric antigen receptor (CAR) T-cell therapy is a novel approach that has demonstrated promising efficacy in the treatment of relapsed, refractory MM (RRMM). These genetically modified cellular therapies have demonstrated deep and durable remissions in other B-cell malignancies, and current efforts aim to achieve similar results in patients with RRMM. Early studies have demonstrated remarkable response rates with CAR T-cell therapy in RRMM; however, durable responses with CAR T-cell therapies in myeloma have yet to be realized. In this comprehensive review, the authors describe the development of CAR T-cell therapies in myeloma, the outcomes of notable clinical trials, the toxicities and limitations of CAR T-cell therapies, and the strategies to overcome therapeutic challenges of CAR T cells in the hope of achieving a cure for multiple myeloma.© 2023 The Authors. CA: A Cancer Journal for Clinicians published by Wiley Periodicals LLC on behalf of American Cancer Society.