Targeting BCMA to Treat Multiple Myeloma: Updates From the 2021 ASH Annual Meeting

Abstract

With the gradual improvement of treatment regimens, the survival time of multiple myeloma (MM) patients has been significantly prolonged. Even so, MM is still a nightmare with an inferior prognosis. B-cell maturation antigen (BCMA) is highly expressed on the surface of malignant myeloma cells. For the past few years, significant progress has been made in various BCMA-targeted immunotherapies for treating patients with RRMM, including anti-BCMA mAbs, antibody-drug conjugates, bispecific T-cell engagers, and BCMA-targeted adoptive cell therapy like chimeric antigen receptor (CAR)-T cell. The 63rd annual meeting of the American Society of Hematology updated some information about the application of BCMA in MM. This review summarizes part of the related points presented at this conference.

Development and manufacture of novel locally produced anti-BCMA CAR T cells for the treatment of relapsed/refractory multiple myeloma: results from a phase I clinical trial

“…Patients' characteristics are detailed in Table 1. The median age was 62 years (range, 44-75), with a median time of 55 months from initial disease diagnosis (range, 8-241) and a median number of 6 previous treatment lines (range, [3][4][5][6][7][8][9][10][11][12][13]. The majority of patients underwent previous autologous bone marrow (BM) transplantation (85%) and all were refractory to proteasome inhibitor (PI), immunomodulatory agent (IMiD), anti-CD38 antibody (daratumumab) and their last treatment line.…”

Molecular and therapeutic effect of CRISPR in treating cancer

“…In case of BCMA, its levels are higher in malignant myeloma cells thus has been a target for immunotherapy including CAR T therapy which is more reliable compared with others. According to American society of hematology (ASH) upon treating with BCMA targeted CAR T therapy there is a promising results on the patients with MM, however more in depth knowledge is needed about the recurrence rate and the long term usage of the therapy so far [ 51 ]. Due to the expression of CD19 in most B cell malignancies, CD19 gene is another targeted gene in CAR T therapy.…”

“…However due to the alloantigens of the recipient T cell therapy endogenous genes/housekeeping genes such as T cell receptor (TCR), and major histocompatibility complex genes (MHC) could lead to graft-versus-host-disease (GVHD) due to HLA-mismatching, which could prevent by CRISPR gene editing, inactivation (knocking out) of endogenous T cell receptor (TCR) genes [ 14 , 27 ]. Based on a research on DLBCL patients TCR and B2M double disrupted CAR T cells therapy by CRISPR, acknowledge the aforementioned problem of GVHD in CAR T cells therapy due to rapid reaction of Human Leukocyte Antigen (HLA) [ 51 ].…”

Anti-BCMA novel therapies for multiple myeloma

“…However, MM patients still do relapse and MM is considered an incurable disease [10,11] . In particular, triple-class refractory (refractory to PI, IMiDs, and anti-CD38 antibody) and penta-refractory (first and second-generation PIs, two generations of IMiDs, anti-CD38 antibody) patients have a median OS of 5.6 months, especially in the presence of high-risk cytogenetics (HR) [12][13][14][15][16][17][18][19][20] or positive minimal residual disease [21][22][23][24][25][26] . Therefore, novel therapies, especially for relapsed/refractory myeloma patients (RRMM), are necessary [25][26] .…”

“…Therefore, novel therapies, especially for relapsed/refractory myeloma patients (RRMM), are necessary [ 25 - 26 ] . BCMA is a B-cell maturation antigen highly expressed in myeloma cells, thus offering an encouraging potential target for novel treatments [ 27 - 28 ] .…”