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Anti-BCMA CAR T-cell therapy in multiple myeloma: can we do better?
Leukemia ( IF 12.8 ) Pub Date : 2019-11-28 , DOI: 10.1038/s41375-019-0669-4
Mattia D'Agostino 1, 2 , Noopur Raje 2
Affiliation  

Despite a substantial survival improvement and the availability of many new drugs in the last 2 decades, multiple myeloma (MM) remains largely incurable. Immunotherapeutic approaches are changing the current landscape in MM with B-cell maturation antigen (BCMA) as one of the most promising target antigens. Chimeric antigen receptor (CAR) T-cell therapy targeting BCMA produced unprecedented results in heavily pretreated relapsed and/or refractory MM. Data on more than 300 MM patients treated with anti-BCMA directed CAR T cells are available and these numbers are rapidly increasing. The response rate and the depth of responses induced by anti-BCMA CAR T cells are impressive; however, the majority of patients eventually relapse. Understanding the underlying mechanisms of response and resistance in treated MM patients will be critical to the rational development of this therapy. Moreover, the ideal place of this therapy in the treatment paradigm for MM is an important question that needs biological and clinical correlative data to help elucidate. T-cell-related, tumor-related and microenvironmental factors may play a role in the efficacy of anti-BCMA CAR T-cell therapy. In this review we summarize key clinical and correlative data on anti-BCMA CAR T-cell therapy. Based on available data we will try to highlight opportunities to further optimize this potential game-changing therapy for MM.

中文翻译:

多发性骨髓瘤的抗 BCMA CAR T 细胞疗法:我们能做得更好吗?

尽管在过去的 20 年里生存率得到了显着改善并且许多新药可用,但多发性骨髓瘤 (MM) 在很大程度上仍然无法治愈。免疫治疗方法正在改变 MM 的现状,B 细胞成熟抗原 (BCMA) 作为最有希望的靶抗原之一。针对 BCMA 的嵌合抗原受体 (CAR) T 细胞疗法在严重预处理的复发和/或难治性 MM 中产生了前所未有的结果。有超过 300 名接受抗 BCMA 定向 CAR T 细胞治疗的 MM 患者的数据可用,而且这些数字正在迅速增加。抗 BCMA CAR T 细胞诱导的反应率和反应深度令人印象深刻;然而,大多数患者最终会复发。了解接受治疗的 MM 患者的反应和抵抗的潜在机制对于该疗法的合理发展至关重要。此外,这种疗法在 MM 治疗范式中的理想位置是一个需要生物学和临床相关数据来帮助阐明的重要问题。T 细胞相关、肿瘤相关和微环境因素可能在抗 BCMA CAR T 细胞疗法的疗效中发挥作用。在这篇综述中,我们总结了抗 BCMA CAR T 细胞疗法的关键临床和相关数据。根据现有数据,我们将尝试强调进一步优化这种潜在的改变 MM 游戏规则的疗法的机会。这种疗法在 MM 治疗范式中的理想位置是一个需要生物学和临床相关数据来帮助阐明的重要问题。T 细胞相关、肿瘤相关和微环境因素可能在抗 BCMA CAR T 细胞疗法的疗效中发挥作用。在这篇综述中,我们总结了抗 BCMA CAR T 细胞疗法的关键临床和相关数据。根据现有数据,我们将尝试强调进一步优化这种潜在的改变 MM 游戏规则的疗法的机会。这种疗法在 MM 治疗范式中的理想位置是一个需要生物学和临床相关数据来帮助阐明的重要问题。T 细胞相关、肿瘤相关和微环境因素可能在抗 BCMA CAR T 细胞疗法的疗效中发挥作用。在这篇综述中,我们总结了抗 BCMA CAR T 细胞疗法的关键临床和相关数据。根据现有数据,我们将尝试强调进一步优化这种潜在的改变 MM 游戏规则的疗法的机会。
更新日期:2019-11-29
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