Non-relapse mortality with bispecific antibodies: A systematic review and meta-analysis in lymphoma and multiple myeloma

Tix, T; Cliff, ERS; Alhomoud, M; Shouval, R; Iacoboni, G; Hansen, DK; Usmani, SZ; Salles, G; Perales, MA; Cordas Dos Santos, DM; Rejeski, K

Author(s): Tix, T; Cliff, ERS; Alhomoud, M; Shouval, R; Iacoboni, G; Hansen, DK; Usmani, SZ; Salles, G; Perales, MA; Cordas Dos Santos, DM; Rejeski, K;
Details: Publication Year 2025-07-02,Volume 33,Issue #7,Page 3163-3176
Journal Title: Molecular Therapy
Publication Type: Review
Abstract: Bispecific antibodies (BsAb) are associated with distinct immune-related toxicities that impact morbidity and mortality. This systematic review and meta-analysis examined non-relapse mortality (NRM) with BsAb therapy in B-cell non-Hodgkin lymphoma (NHL) and multiple myeloma (MM). A PubMed and Embase search up to October 2024 identified 29 studies (21 NHL, 8 MM) involving 2,535 patients. The overall NRM point estimate was 4.7% (95% confidence interval [CI] 3.4%-6.4%), with a median follow-up of 12.0 months. We noted no significant difference in NRM across disease entities (NHL: 4.2%, MM: 6.2%, p = 0.22). In NHL, prespecified subgroup analyses revealed increased NRM in real-world studies compared to clinical trials. For MM, an association between NRM and higher response rates and longer follow-up was noted. Meta-regression comparing BsAb and CAR-T therapies (n = 8,592) showed no significant NRM difference when accounting for key study-level confounders (p = 0.96). Overall, infections were the leading cause of NRM, accounting for 71.8% of non-relapse deaths. Of the infection-related deaths, 48% were attributed to COVID-19. In a pre-specified sensitivity analysis excluding COVID-19 fatalities, the overall NRM estimate was 3.5% (95% CI 2.6%-4.6%). Taken together, these results provide a benchmark for the estimated NRM with BsAb therapy and highlight the paramount importance of infection reporting, prevention, and mitigation.
Publisher: Cell Press
Keywords: Humans; *Antibodies, Bispecific/therapeutic use/adverse effects; *Multiple Myeloma/mortality/drug therapy/therapy/immunology; CAR T-cell therapy; bispecific antibodies; infections; lymphoma; meta-analysis; multiple myeloma; non-relapse mortality
Department(s): Haematology
Publisher's Version: https://doi.org/10.1016/j.ymthe.2025.03.048
Open Access at Publisher's Site: https://doi.org/10.1016/j.ymthe.2025.03.048
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2025-04-10 03:35:25

Last Modified: 2025-08-14 05:00:27