TY - JOUR
T1 - Non-relapse mortality with bispecific antibodies
T2 - A systematic review and meta-analysis in lymphoma and multiple myeloma
AU - Tix, Tobias
AU - Alhomoud, Mohammad
AU - Shouval, Roni
AU - Iacoboni, Gloria
AU - Cliff, Edward R.Scheffer
AU - Hansen, Doris K.
AU - Usmani, Saad Z.
AU - Salles, Gilles
AU - Perales, Miguel Angel
AU - Cordas dos Santos, David M.
AU - Rejeski, Kai
N1 - Publisher Copyright:
© 2025 The Author(s)
PY - 2025/7/2
Y1 - 2025/7/2
N2 - 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.
AB - 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.
KW - CAR T-cell therapy
KW - bispecific antibodies
KW - infections
KW - lymphoma
KW - meta-analysis
KW - multiple myeloma
KW - non-relapse mortality
UR - http://www.scopus.com/inward/record.url?scp=105002765799&partnerID=8YFLogxK
U2 - 10.1016/j.ymthe.2025.03.048
DO - 10.1016/j.ymthe.2025.03.048
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C2 - 40170355
AN - SCOPUS:105002765799
SN - 1525-0016
VL - 33
SP - 3163
EP - 3176
JO - Molecular Therapy
JF - Molecular Therapy
IS - 7
ER -