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

Abstract

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.

T-Cell Receptor Repertoire Sequencing and Its Applications: Focus on Infectious Diseases and Cancer

“…It is possible to distinguish at least two categories of tumor antigens: tumor specific antigens (neoantigen and viral antigen) and tumor associated antigens (cancer/testis (CT) antigen, overexpressed antigen and differentiation antigen) [ 187 ]. The identification and characterization of tumor antigens can lead to the development of therapeutic strategies, such as vaccines and genetically engineered T-cells, particularly CAR-T, which displayed remarkable clinical efficacy in hematological malignancies, with FDA-approved therapies targeting CD19 (Kymriah, Yescarta, Tecartus, Breyanzi) and BCMA (Abecma) [ 188 , 189 , 190 ].…”

Relapsed/Refractory Multiple Myeloma in 2020/2021 and Beyond

“…Investigations on the therapeutic use of CAR-T cells remains the "hot topic" in RRMM also in 2020/2021; several excellent and comprehensive reviews have been published recently (e.g., [53]). Excitingly, CAR T cell treatment is a one-time treatment with the highest efficacy among the novel BCMA-targeting immunotherapeutic options [54].…”

Comparison of FACS and PCR for Detection of BCMA-CAR-T Cells

“…It is the second most frequent hematologic malignancy and remains a largely incurable disease [5]. Novel agents have been approved by the FDA, i.e., proteasome inhibitors (bortezomib, carfilzomib and ixazomib), immunomodulatory drugs (thalidomide, lenalidomide) and lately, monoclonal antibodies such as daratumumab and isatuximab against the CD38 receptor on multiple-myeloma cells and elotuzumab targeting SLAMF7 [6][7][8]. Due to this enrichment of therapeutical diversity, multiplemyeloma patients' median survival duration improved from about 3 to 6 years [7].…”