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


Authors: Tix, T.; Alhomoud, M.; Shouval, R.; Iacoboni, G.; Cliff, E. R. S.; Hansen, D. K.; Usmani, S. Z.; Salles, G.; Perales, M. A.; Cordas dos Santos, D. M.; Rejeski, K.
Review Title: Non-relapse mortality with bispecific antibodies: A systematic review and meta-analysis in lymphoma and multiple myeloma
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. © 2025 The Author(s)
Keywords: multiple myeloma; lymphoma; meta-analysis; infections; bispecific antibodies; non-relapse mortality; car t-cell therapy
Journal Title: Molecular Therapy
Volume: 33
Issue: 7
ISSN: 1525-0016
Publisher: Nature Publishing Group  
Publication status: Published
Date Published: 2025-07-02
Online Publication Date: 2025-01-01
Language: English
DOI: 10.1016/j.ymthe.2025.03.048
PUBMED: 40170355
PROVIDER: scopus
DOI/URL:
Notes: The MSK Cancer Center Support Grant (P30 CA008748) is acknowledge in the PDF -- Corresponding authors is MSK author: Kai Rejeski -- Source: Scopus
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MSK Authors
  1. Miguel-Angel Perales
    935 Perales
  2. Roni Shouval
    167 Shouval
  3. Gilles Andre Salles
    299 Salles
  4. Saad Zafar Usmani
    320 Usmani
  5. Kai Dannebom Rejeski
    30 Rejeski