• Massimo Martino, Filippo Antonio Canale, Caterina Alati, Iolanda Donatella Vincelli, Tiziana Moscato, Gaetana Porto, Barbara Loteta, Virginia Naso, Massimiliano Mazza, Fabio Nicolini, Andrea Ghelli Luserna di Rorà, Giorgia Simonetti, Sonia Ronconi, Michela Ceccolini, Gerardo Musuraca, Giovanni Martinelli, and Claudio Cerchione.
• Stem Cell Transplant and Cellular Therapies Unit, Hemato-Oncology and Radiotherapy Department, Grande OspedaleMetropolitano "Bianchi-Melacrino-Morelli", 89124 Reggio Calabria, RC, Italy.
• Cancers (Basel). 2021 May 27; 13 (11).

AbstractDespite 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.

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