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

in Molecular therapy : the journal of the American Society of Gene Therapy by 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

TLDR

  • This systematic review and meta-analysis found a 4.7% NRM rate with bispecific antibody therapy in NHL and MM patients, with infections being the leading cause of NRM.
  • The study highlights the importance of infection reporting, prevention, and mitigation in reducing NRM rates.
  • Future research is needed to explore risk factors and predictors of NRM and develop strategies to reduce infection-related toxicities.

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% 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.

Overview

  • The study aimed to investigate the non-relapse mortality (NRM) associated with bispecific antibody (BsAb) therapy in patients with B-cell non-Hodgkin lymphoma (NHL) and multiple myeloma (MM).
  • The systematic review and meta-analysis included 29 studies involving 2,535 patients and examined the incidence of NRM during a median follow-up of 12.0 months.
  • The primary objective of the study was to estimate the NRM rate with BsAb therapy and identify potential risk factors and predictors of NRM.

Comparative Analysis & Findings

  • The overall NRM point estimate was 4.7% (95% CI 3.4-6.4%), with 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.

Implications and Future Directions

  • The study highlights the importance of reporting, preventing, and mitigating infection-related toxicities, which were the leading cause of NRM (71.8%).
  • Future research should focus on exploring risk factors and predictors of NRM, as well as developing strategies to reduce infection-related toxicities.
  • A pre-specified sensitivity analysis excluding COVID-19-related fatalities revealed a lower overall NRM estimate of 3.5% (95% CI 2.6-4.6%), emphasizing the need to consider specific circumstances in interpreting NRM rates.
Read Full Article