Struttura Semplice Dipartimentale di Oncologia Medica per la Presa in Carico Globale del Paziente Oncologico "Don Tonino Bello", Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS), Istituto Tumori Giovanni Paolo II-Bari, Viale Orazio Flacco 65, 70124, Bari, Italy.
Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni-15, 40138, Bologna, Italy.
Cancer Immunol Immunother. 2023 Jun;72(6):1381-1394. doi: 10.1007/s00262-023-03366-x. Epub 2023 Jan 25.
The antitumor efficacy of immune checkpoint inhibitors (ICIs) has increasingly emerged during the last few years. However, there is a need to identify the safety profile of these agents more comprehensively, including liver toxicity.
Herein, we performed a meta-analysis to assess the risk of all-grade and grade 3-4 hypertransaminasemia in cancer patients receiving ICIs-as monotherapy or in combination with other anticancer agents. All the relevant trials were retrieved through EMBASE, Cochrane Library, and PubMed/Medline databases; eligible studies were selected according to PRISMA statement. The pooled relative risk (RR) and 95% confidence interval (CI) were extracted.
Fifty-nine studies were included. The pooled RRs for all-grade AST and ALT increase were 1.45 (95% CI 1.26-1.67) (Supplementary Fig. 3) and 1.51 (95% CI 1.29-1.77) in patients receiving ICIs monotherapy and immune-based combinations compared to control treatment, respectively. The pooled RRs for grade 3-4 AST and ALT increase were 2.16 (95% CI 1.77-2.64) and 2.3 (95% CI 1.91-2.77).
According to our results, ICIs monotherapy and immune-based combinations were associated with higher risk of all-grade and grade 3-4 hypertransaminasemia. Monitoring liver function should be recommended in cancer patients treated with ICIs monotherapy or immune-based combination, and in case of underlying liver disease, a careful risk-benefit assessment appears as a mandatory need.
在过去的几年中，免疫检查点抑制剂（ICIs）的抗肿瘤疗效日益显现。然而，需要更全面地确定这些药物的安全性概况，包括肝毒性。
在此，我们进行了一项荟萃分析，以评估接受 ICI 单药治疗或与其他抗癌药物联合治疗的癌症患者发生所有级别和 3-4 级高转氨酶血症的风险。通过 EMBASE、Cochrane 图书馆和 PubMed/Medline 数据库检索所有相关试验；根据 PRISMA 声明选择合格的研究。提取了合并的相对风险（RR）和 95%置信区间（CI）。
共纳入 59 项研究。与对照组相比，ICI 单药治疗和免疫联合治疗的患者发生所有级别 AST 和 ALT 升高的合并 RR 分别为 1.45（95%CI 1.26-1.67）（补充图 3）和 1.51（95%CI 1.29-1.77）。ICI 单药治疗和免疫联合治疗的患者发生 3-4 级 AST 和 ALT 升高的合并 RR 分别为 2.16（95%CI 1.77-2.64）和 2.3（95%CI 1.91-2.77）。
根据我们的结果，ICI 单药治疗和免疫联合治疗与所有级别和 3-4 级高转氨酶血症的风险增加相关。建议对接受 ICI 单药治疗或免疫联合治疗的癌症患者监测肝功能，对于存在潜在肝病的患者，需要谨慎评估风险效益比。
