Venetoclax 联合疗法治疗复发/难治性急性髓系白血病的疗效和安全性：系统评价和荟萃分析。

BACKGROUND: As we delve into the intricate world of venetoclax combination therapy in relapsed or refractory acute myeloid leukemia (AML), our exploration not only aims to contribute to the current body of knowledge but also strives to inform future research directions, clinical decision-making, and the ongoing evolution of therapeutic strategies in the relentless pursuit of improved outcomes for patients facing this formidable hematologic malignancy. METHODS: We systematically searched PubMed, Embase, and Cochrane databases from inception to November 2023 for English-language studies on venetoclax combination therapy in relapsed/refractory AML. We excluded duplicate published studies, incomplete studies, those with incomplete data, animal experiments, literature reviews, and systematic studies. Meta-analysis was performed using STATA 15.1. RESULTS: Out of 58 identified articles, seven were included in the meta-analysis. The pooled complete remission (CR) rate was 15.4%, and the composite complete remission (CRc) rate was 35.7%. The partial remission (PR) rate was 2.6%, while the non-remission (NR) rate was 24.4%. The minimal residual disease status in CRc patients (MRD-CRc) rate was 39.4%, and the morphologic leukemia-free state (MLFS) rate was 10.3%. Incidence of adverse events included diarrhea (10.0%), nausea (4.3%), vomiting (2.6%), hypokalemia (16.4%), hypomagnesemia (0.8%), decreased appetite (4.2%), fatigue (9.1%), febrile neutropenia (39.6%), and thrombocytopenia (28.4%). Subgroup analysis based on combined drugs revealed varying CR and CRc rates. the combination of venetoclax and azacitidine + demonstrates superior outcomes, displaying the highest rates of CR at 31.3% and CRc at 62.7%. In contrast, venetoclax and idasanutlin exhibits a moderate CR rate of 6.1% and a CRc rate of 26.5%, while venetoclax and mivebresib shows the lowest CR rate at 3.3% and a moderate CRc rate of 8.0%. CONCLUSION: In conclusion, while venetoclax combination therapies, particularly with azacitidine + , show promise in achieving favorable treatment responses in relapsed/refractory AML patients, a comprehensive evaluation of safety profiles is essential. Nevertheless, it is essential to underscore the markedly increased incidence rates of febrile neutropenia and thrombocytopenia observed among adverse events.

背景：在深入研究 Venetoclax 联合治疗复发/难治性急性髓系白血病（AML）的过程中，我们的探索不仅旨在为现有知识体系做出贡献，还力求为未来的研究方向、临床决策以及治疗策略的不断发展提供信息，以不断提高面临这一严峻血液恶性肿瘤患者的治疗效果。

方法：我们系统地检索了 PubMed、Embase 和 Cochrane 数据库，检索时间从建库至 2023 年 11 月，检索对象为英文文献中 Venetoclax 联合治疗复发/难治性 AML 的研究。我们排除了重复发表的研究、不完整的研究、数据不完整的研究、动物实验、文献综述和系统研究。使用 STATA 15.1 进行荟萃分析。

结果：在 58 篇已识别的文章中，有 7 篇被纳入荟萃分析。完全缓解（CR）率的合并值为 15.4%，复合完全缓解（CRc）率为 35.7%。部分缓解（PR）率为 2.6%，未缓解（NR）率为 24.4%。CRc 患者的微小残留病状态（MRD-CRc）率为 39.4%，形态学白血病无状态（MLFS）率为 10.3%。不良事件的发生率包括腹泻（10.0%）、恶心（4.3%）、呕吐（2.6%）、低钾血症（16.4%）、低镁血症（0.8%）、食欲减退（4.2%）、疲劳（9.1%）、发热性中性粒细胞减少症（39.6%）和血小板减少症（28.4%）。基于联合用药的亚组分析显示，CR 和 CRc 的发生率存在差异。Venetoclax 联合阿扎胞苷+的疗效最佳，CR 率为 31.3%，CRc 率为 62.7%。相比之下，Venetoclax 联合伊达司他林的 CR 率为 6.1%，CRc 率为 26.5%，而 Venetoclax 联合米伏雷司布的 CR 率最低，为 3.3%，CRc 率为 8.0%。

结论：综上所述，Venetoclax 联合治疗，特别是联合阿扎胞苷+，在复发/难治性 AML 患者中显示出良好的治疗反应，但全面评估安全性至关重要。然而，必须强调的是，中性粒细胞减少症和血小板减少症等不良事件发生率明显增加。