尽管嵌合抗原受体 (CAR) T 细胞疗法代表了一种变革性免疫疗法，但它也与导致发病率和死亡率的独特毒性有关。在这项系统回顾和荟萃分析中，我们检索了 MEDLINE、Embase 和 CINAHL (Cochrane)，查找截至 2024 年 3 月 CAR T 细胞治疗淋巴瘤和多发性骨髓瘤后非复发死亡率 (NRM) 的报告。提取死亡原因和死亡人数后，我们使用随机效应模型分析了 NRM 点估计。我们通过 18 项临床试验和 28 项真实世界研究确定了 7,604 名患者。 NRM 点估计值因疾病实体而异，套细胞淋巴瘤患者最高（10.6%），其次是多发性骨髓瘤（8.0%）、大 B 细胞淋巴瘤（6.1%）和惰性淋巴瘤（5.7%）。大 B 细胞淋巴瘤和多发性骨髓瘤的实体特异性元回归模型显示，axicabtagene ciloleucel 和 ciltacabtagene autoleucel 分别与 NRM 点估计值增加独立相关。在 574 例报告的非复发性死亡中，一半以上归因于感染 (50.9%)，其次是其他恶性肿瘤 (7.8%) 和心血管/呼吸系统事件 (7.3%)。相反，CAR T 细胞特异性副作用、免疫效应细胞相关神经毒性综合征/神经毒性、细胞因子释放综合征和噬血细胞性淋巴组织细胞增多症仅占非复发死亡的一小部分（累计占 11.5%）。我们的研究结果强调了 CAR T 细胞治疗后感染并发症的重要性，并支持 NRM 的综合报告，包括具体原因和长期结果。© 2024。作者获得 Springer Nature America, Inc. 的独家许可。

Although chimeric antigen receptor (CAR) T cell therapy represents a transformative immunotherapy, it is also associated with distinct toxicities that contribute to morbidity and mortality. In this systematic review and meta-analysis, we searched MEDLINE, Embase and CINAHL (Cochrane) for reports of nonrelapse mortality (NRM) after CAR T cell therapy in lymphoma and multiple myeloma up to March 2024. After extraction of causes and numbers of death, we analyzed NRM point estimates using random-effect models. We identified 7,604 patients across 18 clinical trials and 28 real-world studies. NRM point estimates varied across disease entities and were highest in patients with mantle-cell lymphoma (10.6%), followed by multiple myeloma (8.0%), large B cell lymphoma (6.1%) and indolent lymphoma (5.7%). Entity-specific meta-regression models for large B cell lymphoma and multiple myeloma revealed that axicabtagene ciloleucel and ciltacabtagene autoleucel were independently associated with increased NRM point estimates, respectively. Of 574 reported nonrelapse deaths, over half were attributed to infections (50.9%), followed by other malignancies (7.8%) and cardiovascular/respiratory events (7.3%). Conversely, the CAR T cell-specific side effects, immune effector cell-associated neurotoxicity syndrome/neurotoxicity, cytokine release syndrome and hemophagocytic lymphohistiocytosis, represented only a minority of nonrelapse deaths (cumulatively 11.5%). Our findings underline the critical importance of infectious complications after CAR T cell therapy and support the comprehensive reporting of NRM, including specific causes and long-term outcomes.© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.