CART-Cell Therapy: Recent Advances and New Evidence in Multiple Myeloma

被引：26

作者：

Martino, Massimo ^{[1
]}

Canale, Filippo Antonio ^{[1
]}

Alati, Caterina ^{[2
]}

Vincelli, Iolanda Donatella ^{[2
]}

Moscato, Tiziana ^{[1
]}

Porto, Gaetana ^{[1
]}

Loteta, Barbara ^{[1
]}

Naso, Virginia ^{[1
]}

Mazza, Massimiliano ^{[3
]}

Nicolini, Fabio ^{[3
]}

Ghelli Luserna di Rora, Andrea ^{[4
]}

Simonetti, Giorgia ^{[4
]}

Ronconi, Sonia ^{[5
]}

Ceccolini, Michela ^{[5
]}

Musuraca, Gerardo ^{[5
]}

Martinelli, Giovanni ^{[5
]}

Cerchione, Claudio ^{[5
]}

机构：

[1] Grande Osped Metropolitano Bianchi Melacrino More, Hematooncol & Radiotherapy Dept, Stem Cell Transplant & Cellular Therapies Unit, I-89124 Reggio Di Calabria, RC, Italy

[2] Grande Osped Metropolitano Bianchi Melacrino More, Hematooncol & Radiotherapy Dept, Hematol Unit, I-89124 Reggio Di Calabria, RC, Italy

[3] IRCCS Ist Romagnolo Tumori IRST Dino Amadori, Cell Therapy & Biobank ITCB, Immunotherapy, I-47014 Meldola, FC, Italy

[4] IRCCS Ist Romagnolo Tumori IRST Dino Amadori, Biosci Lab, I-47014 Meldola, FC, Italy

[5] IRCCS Ist Romagnolo Tumori IRST Dino Amadori, Hematol Unit, I-47014 Meldola, FC, Italy

来源：

CANCERS | 2021年 / 13卷 / 11期

关键词：

multiple myeloma; BCMA; CAR T; relapsed multiple myeloma; refractory myeloma; cytokine release syndrome; neurologic toxicity; MATURATION ANTIGEN BCMA; RECEPTOR T-CELLS; CHIMERIC ANTIGEN; PATIENTS PTS; IMMUNOTHERAPY; PHASE-1; EFFICACY; FUTURE; SAFETY; DARATUMUMAB;

D O I：

10.3390/cancers13112639

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Simple Summary 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 CAR T therapy is safety. Cytokine release syndrome (CRS) and neurologic toxicity are well-described adverse effects. In MM trials, most CRS events tended to be grade 1 or 2. Another critical point is the extended timeline of the manufacturing process and that 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. 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.

引用

页数：19