Efficacy and safety of bispecific antibodies therapy for relapsed or refractory multiple myeloma: a systematic review and meta-analysis of prospective clinical trials

Abstract

Objective: Bispecific antibody (BsAbs) therapy represents a promising immunotherapeutic approach with manageable toxicity and noteworthy preliminary efficacy in treating patients with relapsed or refractory multiple myeloma (RRMM). The objective of this systematic review and meta-analysis was to compare the efficacy and safety of B-cell maturation antigen (BCMA)-targeted BsAbs and non-BCMA-targeted BsAbs in the treatment of RRMM patients.

Methods: PubMed/MEDLINE, Web of Science, EMBASE, Cochrane Library and meeting libraries were searched from inception to August 16th, 2023. The efficacy evaluation included the complete objective response rate (ORR), complete response (CR) rate, stringent CR (sCR) rate, partial response (PR) rate, and very good PR (VGPR) rate. The efficacy evaluation included any grade adverse events (AEs) and grade ≥ 3 AEs.

Results: Fourteen studies with a total of 1473 RRMM patients were included. The pooled ORR of the entire cohort was 61%. The non-BCMA-targeted BsAbs group displayed a higher ORR than the BCMA-targeted BsAbs group (74% vs. 54%, P < 0.01). In terms of hematological AEs, BCMA-targeted BsAbs therapy exhibited higher risks of neutropenia (any grade: 48% vs. 18%, P < 0.01; grade ≥ 3: 43% vs. 15%, P < 0.01) and lymphopenia (any grade: 37% vs. 8%, P < 0.01; grade ≥ 3: 31% vs. 8%, P = 0.07). Regarding non-hematological AEs, there were no significant differences in the risks of cytokine release syndrome (CRS, any grade: 64% vs. 66%, P = 0.84; grade ≥ 3: 1% vs. 1%, P = 0.36) and infections (any grade: 47% vs. 49%, P = 0.86; grade ≥ 3: 24% vs. 20%, P = 0.06) between the two groups. However, non-BCMA-targeted BsAbs therapy was associated with a higher risk of immune effector cell-associated neurotoxicity syndrome (ICANS, any grade: 11% vs. 2%, P < 0.01) and lower risks of fatigue (any grade: 14% vs. 30%, P < 0.01) and pyrexia (any grade: 14% vs. 29%, P < 0.01).

Conclusion: This analysis suggest that non-BCMA-targeted BsAbs therapy may offer a more favorable treatment response and tolerability, while BCMA-targeted BsAbs therapy may be associated with diminished neurotoxic effects.

Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42018090768.

Keywords: bispecific antibodies; efficacy; immunotherapy; multiple myeloma; safety.

Figure 1

The flow chart.

Figure 2

The pooled (A) ORR, (B) sCR, (C) CR, (D) PR, (E) VGPR and (F) ≥VGPR in patients treated with BsAbs. 1) The two dose cohorts in the trial of linvoseltamab were analyzed separately: (a) 50 mg and (b) 200 mg. 2) The two dose cohorts in the trial of TNB-383B were analyzed separately: (c) 40 mg and (d) 60 mg. 3) The two usage cohorts in the trial of alnuctamab were separately analyzed separately: (e) intravenous and (f) subcutaneous administration. 4) The different doses and groups of patient cohorts in the trial of talquetamab were analyzed separately: (g) 0.4 mg/kg; previous treatment with T-cell redirection therapy was not allowed, (h) 0.8 mg/kg; previous treatment with a T-cell redirection therapy was not allowed, and (i) 0.4 mg/kg or 0.8 mg/kg; patients enrolled had prior exposure to T-cell redirection therapy. 5) The two usage cohorts in the trial of RG6234 were analyzed separately: (j) intravenous and (k) subcutaneous administration.

Figure 3

The pooled risks of any grade (A) anemia, (B) neutropenia, (C) thrombocytopenia and (D) lymphopenia in patients treated with BsAbs. 1) The two dose cohorts in the trial of linvoseltamab were analyzed separately: (a) 50 mg and (b) 200 mg. 2) The two dose cohorts in the trial of TNB-383B were analyzed separately: (c) 40 mg and (d) 60 mg. 3) The (f) subcutaneous administration cohort in the trial of alnuctamab was analyzed separately.

Figure 4

The pooled risk of grade ≥ 3 (A) anemia, (B) neutropenia, (C) thrombocytopenia and (D) lymphopenia in patients treated with BsAbs. 1) The two dose cohorts in the trial of linvoseltamab were analyzed separately: (a) 50 mg and (b) 200 mg. 2) The two dose cohorts in the trial of TNB-383B were analyzed separately: (c) 40 mg and (d) 60 mg. 3) The (f) subcutaneous administration cohort in the trial of alnuctamab was analyzed separately. 4) The two usage cohorts in the trial of RG6234 were analyzed separately: (j) intravenous and (k) subcutaneous administration.

Figure 5

The pooled risks of (A) any grade CRS, (B) grade ≥ 3 CRS, (C) any grade infections, and (D) grade ≥ 3 infections in patients treated with BsAbs. 1) The two dose cohorts in the trial of linvoseltamab were analyzed separately: (a) 50 mg and (b) 200 mg. 2) The two dose cohorts in the trial of TNB-383B were analyzed separately: (c) 40 mg and (d) 60 mg. 3) The (f) subcutaneous administration cohort in the trial of alnuctamab was analyzed separately. 4) The different doses and groups of patient cohorts in the trial of talquetamab were analyzed separately: (g) 0.4 mg/kg; previous treatment with T-cell redirection therapy was not allowed, (h) 0.8 mg/kg; previous treatment with a T-cell redirection therapy was not allowed, and (i) 0.4 mg/kg or 0.8 mg/kg; patients enrolled had prior exposure to T-cell redirection therapy. 5) The two usage cohorts in the trial of RG6234 were analyzed separately: (j) intravenous and (k) subcutaneous administration.