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, Rejeski Kai
Department of Medicine III - Hematology/Oncology, LMU University Hospital, LMU Munich, Munich, Germany.
Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Mol Ther. 2025 Jul 2;33(7):3163-3176. doi: 10.1016/j.ymthe.2025.03.048. Epub 2025 Mar 31.
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.
双特异性抗体（BsAb）与影响发病率和死亡率的独特免疫相关毒性有关。本系统评价和荟萃分析研究了BsAb治疗B细胞非霍奇金淋巴瘤（NHL）和多发性骨髓瘤（MM）时的非复发死亡率（NRM）。截至2024年10月的PubMed和Embase检索共识别出29项研究（21项NHL研究，8项MM研究），涉及2535例患者。NRM的总体点估计值为4.7%（95%置信区间[CI] 3.4%-6.4%），中位随访时间为12.0个月。我们注意到不同疾病实体的NRM无显著差异（NHL：4.2%，MM：6.2%，p = 0.22）。在NHL中，预先设定的亚组分析显示，与临床试验相比，真实世界研究中的NRM有所增加。对于MM，注意到NRM与更高的缓解率和更长的随访时间之间存在关联。比较BsAb和CAR-T疗法（n = 8592）的Meta回归显示，在考虑关键研究水平的混杂因素时，NRM无显著差异（p = 0.96）。总体而言，感染是NRM的主要原因，占非复发死亡的71.8%。在与感染相关的死亡中，48%归因于COVID-19。在一项排除COVID-19死亡病例的预先设定的敏感性分析中，NRM的总体估计值为3.5%（95% CI 2.6%-4.6%）。综上所述，这些结果为BsAb治疗的估计NRM提供了一个基准，并突出了感染报告、预防和缓解的至关重要性。
