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

Tix, Tobias; Alhomoud, Mohammad; Shouval, Roni; Iacoboni, Gloria ; Cliff, Edward R. Scheffer; Hansen, Doris K.; Usmani, Saad Z.; Salles, Gilles; Perales, Miguel-Angel; Cordas dos Santos, David M. und Rejeski, Kai (2025): Non-relapse mortality with bispecific antibodies: A systematic review and meta-analysis in lymphoma and multiple myeloma. In: Molecular Therapy, Bd. 33, Nr. 7: S. 3163-3176

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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin > Klinikum der LMU München > Medizinische Klinik und Poliklinik III (Onkologie)
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 15250016
• Sprache: Englisch
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 525171148