The Role of Bispecific Antibodies in Relapsed Refractory Multiple Myeloma: A Systematic Review

Abstract

Multiple myeloma is a heterogeneous clonal malignant plasma cell disorder, which remains incurable despite the therapeutic armamentarium’s evolution. Bispecific antibodies (BsAbs) can bind simultaneously to the CD3 T-cell receptor and tumor antigen of myeloma cells, causing cell lysis. This systematic review of phase I/II/III clinical trials aimed to analyze the efficacy and safety of BsAbs in relapsed refractory multiple myeloma (RRMM). A thorough literature search was performed using PubMed, Cochrane Library, EMBASE, and major conference abstracts. A total of 18 phase I/II/III studies, including 1283 patients, met the inclusion criteria. Among the B-cell maturation antigen (BCMA)-targeting agents across 13 studies, the overall response rate (ORR) ranged between 25% and 100%, with complete response/stringent complete response (CR/sCR) between 7 and 38%, very good partial response (VGPR) between 5 and 92%, and partial response (PR) between 5 and 14%. Among the non-BCMA-targeting agents across five studies, the ORR ranged between 60 and 100%, with CR/sCR seen in 19–63%, and VGPR in 21–65%. The common adverse events were cytokine release syndrome (17–82%), anemia (5–52%), neutropenia (12–75%), and thrombocytopenia (14–42%). BsAbs have shown promising efficacy against RRMM cohorts with a good safety profile. Upcoming phase II/III trials are much awaited, along with the study of other agents in concert with BsAbs to gauge response.

Use of venetoclax in t(11;14) positive relapsed/refractory multiple myeloma: A systematic review

“…For this reason, the anti-apoptotic protein has become one of the more promising routes and an ideal target for cancer treatment. 18…”

Progressive Multifocal Leukoencephalopathy Unmasked by Teclistamab in a Refractory Multiple Myeloma Patient

“…Teclistamab, a bispecific antibody, functions by targeting both BCMA (B-cell maturation antigen) on myeloma cells and CD3 on T-cells [1,2]. This dual targeting mechanism facilitates a robust cytotoxic T-cell response against the myeloma cells, a crucial aspect in its action against relapsed or refractory multiple myeloma (MM) [1].…”

“…Teclistamab, a bispecific antibody, functions by targeting both BCMA (B-cell maturation antigen) on myeloma cells and CD3 on T-cells [1,2]. This dual targeting mechanism facilitates a robust cytotoxic T-cell response against the myeloma cells, a crucial aspect in its action against relapsed or refractory multiple myeloma (MM) [1]. In relapsed or refractory MM, teclistamab has shown high rates of response, with clinical trials indicating a substantial proportion of patients achieving complete or very good partial responses (VGPR) [3].…”

Bi- and trispecific immune cell engagers for immunotherapy of hematological malignancies

“…In this review, we will discuss antibody formats, immunologic background, mechanisms of action, relevant clinical and preclinical literature and future perspectives of BsAb and TsAb aimed to redirect T cells and NK cells toward hematological malignancies. A detailed account of the clinical data and side effects would go beyond the scope of this review and we would like to refer the reader to previously published studies [ 2 – 6 ].…”