Non-relapse mortality with bispecific antibodies: A systematic review and meta-analysis in lymphoma and multiple myeloma
Tobias Tix, Mohammad Alhomoud, Roni Shouval, Gloria Iacoboni, Edward R. Scheffer Cliff, Doris K. Hansen, Saad Z. Usmani, Gilles Salles, Miguel‐Angel Perales, David M. Cordas dos Santos, Kai Rejeski
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.