Martino Massimo, Canale Filippo Antonio, Alati Caterina, Vincelli Iolanda Donatella, Moscato Tiziana, Porto Gaetana, Loteta Barbara, Naso Virginia, Mazza Massimiliano, Nicolini Fabio, Ghelli Luserna di Rorà Andrea, Simonetti Giorgia, Ronconi Sonia, Ceccolini Michela, Musuraca Gerardo, Martinelli Giovanni, Cerchione Claudio
Stem Cell Transplant and Cellular Therapies Unit, Hemato-Oncology and Radiotherapy Department, Grande OspedaleMetropolitano "Bianchi-Melacrino-Morelli", 89124 Reggio Calabria, RC, Italy.
Hematology Unit, Hemato-Oncology and Radiotherapy Department, Grande Ospedale Metropolitano "Bianchi-Melacrino-Morelli", 89124 Reggio Calabria, RC, Italy.
Cancers (Basel). 2021 May 27;13(11):2639. doi: 10.3390/cancers13112639.
Despite the improvement in survival outcomes, multiple myeloma (MM) remains an incurable disease. Chimeric antigen receptor (CAR) T-cell therapy targeting B-cell maturation antigen (BCMA) represents a new strategy for the treatment of relapsed/refractory MM (R/R). In this paper, we describe several recent advances in the field of anti-BCMA CAR T-cell therapy and MM. Currently, available data on anti-BCMA CART-cell therapy has demonstrated efficacy and manageable toxicity in heavily pretreated R/R MM patients. Despite this, the main issues remain to be addressed. First of all, a significant proportion of patients eventually relapse. The potential strategy to prevent relapse includes sequential or combined infusion with CAR T-cells against targets other than BCMA, CAR T-cells with novel dual-targeting vector design, and BCMA expression upregulation. Another dark side of CART therapy is safety. Cytokine release syndrome (CRS) andneurologic toxicity are well-described adverse effects. In the MM trials, most CRS events tended to be grade 1 or 2, with fewer patients experiencing grade 3 or higher. Another critical point is the extended timeline of the manufacturing process. Allo-CARs offers the potential for scalable manufacturing for on-demand treatment with shorter waiting days. Another issue is undoubtedly going to be access to this therapy. Currently, only a few academic centers can perform these procedures. Recognizing these issues, the excellent response with BCMA-targeted CAR T-cell therapy makes it a treatment strategy of great promise.
尽管生存结果有所改善,但多发性骨髓瘤(MM)仍然是一种无法治愈的疾病。靶向B细胞成熟抗原(BCMA)的嵌合抗原受体(CAR)T细胞疗法代表了一种治疗复发/难治性MM(R/R)的新策略。在本文中,我们描述了抗BCMA CAR T细胞疗法和MM领域的几项最新进展。目前,关于抗BCMA CART细胞疗法的现有数据已证明在经过大量预处理的R/R MM患者中具有疗效且毒性可控。尽管如此,主要问题仍有待解决。首先,相当一部分患者最终会复发。预防复发的潜在策略包括与针对BCMA以外靶点的CAR T细胞序贯或联合输注、具有新型双靶点载体设计的CAR T细胞以及上调BCMA表达。CART疗法的另一个不利方面是安全性。细胞因子释放综合征(CRS)和神经毒性是已充分描述的不良反应。在MM试验中,大多数CRS事件倾向于1级或2级,经历3级或更高等级的患者较少。另一个关键点是制造过程的时间延长。同种异体CARs为按需治疗提供了可扩展制造的潜力,等待天数更短。另一个问题无疑将是这种疗法的可及性。目前,只有少数学术中心能够开展这些程序。认识到这些问题,靶向BCMA的CAR T细胞疗法的出色反应使其成为一种极具前景的治疗策略。