目的 基于美国食品药品监督管理局（FDA）不良事件报告系统（FAERS）数据库分析B细胞成熟抗原（BCMA）双抗埃纳妥单抗（elranatamab）真实世界安全性，并与特立妥单抗（teclistamab）比较，优化全球药物警戒策略。方法采用比例失衡分析法（ROR/PRR）联合贝叶斯置信传播神经网络（BCPNN）对717例首要怀疑埃纳妥单抗报告（2023年第一季度—2025年第一季度）进行三角验证。信号判定标准：（1）报告数≥3；（2） ROR/PRR 95%置信区间（CI）下限＞ 1（χ²＞4）且信息成分（IC₀₂₅）下限＞0；（3）排除适应证相关首选术语（PT）及非药物相关系统器官分类（SOC）。结果识别出8个（5.0%）说明书未收录的潜在信号，包括高强度机会性感染（腺病毒性肝炎ROR 619.9，95% CI： 185.95～2 066.53；巨细胞病毒性胃肠炎ROR 594.07，95% CI： 178.72～1 974.71；中位发生时间26 d）及心脏毒性（心力衰竭ROR 12.74）等。尽管信号强度高，但因报告数较少（a＝3），其绝对风险尚需大样本研究进一步确认。机会性感染与低丙种球蛋白血症（ROR 67.93）共同支持“BCMA靶向治疗免疫监视缺陷”假说。结论 多方法验证揭示埃纳妥单抗突破传统CRS/ICANS框架的多系统毒性（尤其机会性感染及器官特异性毒性），为免疫监视缺陷理论提供关键证据。较特立妥单抗，两者机会性感染风险相似，但心脏毒性谱存在显著差异，需整合CNADR数据库验证东亚人群种族差异风险。

Objective To analyze the real-world safety profile of the BCMA-targeted bispecific antibody elranatamab using the FDA Adverse Event Reporting System (FAERS) database, with comparative assessment against teclistamab, to optimize global pharmacovigilance strategies. Methods A triangulated approach employing disproportionality analysis [Reporting Odds Ratio (ROR)/Proportional Reporting Ratio (PRR) ] alongside the Bayesian Confidence Propagation Neural Network (BCPNN) was applied to 717 primary suspect reports of elranatamab (Q1 2023—Q1 2025). Signal detection criteria required: ① ≥ 3 reports; ② Lower bound of the 95% confidence interval for ROR/PRR >1 (χ² > 4)and IC025 > 0; ③ Exclusion of Preferred Terms (PTs) related to the drug’s indication and System Organ Classes (SOCs) unrelated to drug effects. Results Eight (5.0%) potentially unlisted signals in the drug label were identified, including high-intensity opportunistic infections (adenoviral hepatitis: ROR 619.9, 95% CI: 185.95—2 066.53; cytomegalovirus gastroenteritis: ROR 594.07, 95% CI: 178.72—1 974.71; median onset time 26 d) and cardiotoxicity (heart failure: ROR 12.74), among others. Despite the high signal strength, the absolute risk requires further confirmation by large-scale studies due to the small number of reports (a = 3). The co-occurrence of opportunistic infections with hypogammaglobulinemia (ROR 67.93) supports the hypothesis of “immune surveillance deficiency induced by BCMA-targeted therapy”. Conclusion Multi-method validation revealed elranatamab's multi-system toxicities extending beyond the conventional CRS/ICANS framework (notably opportunistic infections and organ-specific toxicities), providing key evidence supporting the immune surveillance deficiency theory. Compared with teclistamab, while both agents demonstrate comparable risks of opportunistic infections, marked differences exist in their cardiotoxicity profiles. Integration with China’s National Adverse Drug Reaction Monitoring System (CNADR) database is warranted to validate ethnic-specific risks in East Asian populations.

R979.1

吴阶平医学基金会临床科研专项资助基金项目（320.6750.2024-18-31）