晚期非小细胞肺癌患者免疫治疗血液学不良事件≥3级：系统回顾和荟萃分析

IF 2.4 3区医学 Q3 PHARMACOLOGY & PHARMACY

European Journal of Clinical Pharmacology Pub Date : 2025-01-22 DOI:10.1007/s00228-025-03803-z

Shuang Wang, Mengting Cai, Yajun Xiong, Tianyi Guo, Xiaoya Niu, Yu Chen, Yuying Feng, Chunhua Song, Aiguo Xu

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引用次数: 0

摘要

背景：在标准化疗中加入免疫检查点抑制剂（ICIs）对晚期非小细胞肺癌（NSCLC）患者骨髓抑制的严重程度和风险的影响仍不确定。方法：我们对评估非小细胞肺癌患者ICIs的3期随机对照试验（rct）进行了系统回顾和荟萃分析。从成立到2023年10月30日，对PubMed、Web of Science、Embase和Cochrane Library四个数据库进行了全面搜索。合并分析评估治疗相关血液学不良事件大于或等于3级的风险比（RR）。该协议在PROSPERO注册，注册号为CRD42024500056。研究结果：共纳入23项3期随机对照试验，涉及15844例接受ICIs伴或不伴化疗的NSCLC患者。与单独化疗相比，ICI单药或双重免疫治疗降低了治疗相关的白细胞减少（相对危险度（RR） 0.03, 95% CI 0.01-0.08）、中性粒细胞减少（RR 0.02, 95% CI 0.01-0.03）、血小板减少（RR 0.05, 95% CI 0.02-0.14）和贫血（RR 0.09, 95% CI 0.05-0.15），合并发病率分别为0.07%、0.08%、0.14%和9.07%。与单独化疗相比，ICIs联合化疗增加了发生治疗相关性血小板减少症的风险（RR 1.35, 95% CI 1.04-1.77），合并发病率为6.83%；它没有增加白细胞减少症（RR 0.97, 95% CI 0.70-1.35）、中性粒细胞减少症（RR 1.05, 95% CI 0.90-1.23）和贫血（RR 1.10, 95% CI 0.85-1.43），合并发病率分别为4.47%、14.67%和13.36%。解释：对于晚期或转移性NSCLC患者，与化疗相比，单独使用ICIs时，严重的血液学不良事件并不常见。然而，当与化疗联合使用时，这些副作用可能会加剧，特别是以3级或更高级别血小板减少发生率升高的形式。

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Grade ≥ 3 hematologic adverse events of immunotherapy in advanced NSCLC patients: a systematic review and meta-analysis.

Background: The impact of incorporating immune checkpoint inhibitors (ICIs) into standard chemotherapy on the severity and risk of myelosuppression in advanced non-small cell lung cancer (NSCLC) patients remains uncertain.

Methods: We conducted a systematic review and meta-analysis of phase 3 randomized controlled trials (RCTs) that evaluated ICIs in people with NSCLC. A comprehensive search of four databases, PubMed, Web of Science, Embase, and the Cochrane Library, was carried out from inception to 30 October 2023. Pooled analyses assessed the risk ratios (RR) for treatment-related hematological adverse events greater than or equal to grade 3. The protocol is registered with PROSPERO and has the CRD42024500056 registration number.

Findings: Twenty-three phase 3 RCTs were contained, involving 15,844 people with NSCLC receiving ICIs with or without chemotherapy. Compared with chemotherapy alone, ICI monotherapy or dual immunotherapy reduced treatment-associated leukopenia (relative risk (RR) 0.03, 95% CI 0.01-0.08), neutropenia (RR 0.02, 95% CI 0.01-0.03), thrombocytopenia (RR 0.05, 95% CI 0.02-0.14), and anemia (RR 0.09, 95% CI 0.05-0.15), with a pooled incidence of 0.07%, 0.08%, 0.14%, and 9.07%. Compared with chemotherapy alone, ICIs in combination with chemotherapy increased the risk of developing treatment-related thrombocytopenia (RR 1.35, 95% CI 1.04-1.77), with a pooled incidence rate of 6.83%; it did not increase leukopenia (RR 0.97, 95% CI 0.70-1.35), neutropenia (RR 1.05, 95% CI 0.90-1.23), and anemia (RR 1.10, 95% CI 0.85-1.43), with pooled incidence rates of 4.47%, 14.67%, and 13.36%, respectively.

Interpretation: For patients with advanced or metastatic NSCLC, severe hematological adverse events are uncommon when ICIs are used alone, as opposed to chemotherapy. However, when used in conjunction with chemotherapy, these side effects may be intensified, particularly in the form of an elevated incidence of thrombocytopenia of grade 3 or higher.

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来源期刊

European Journal of Clinical Pharmacology 医学-药学

CiteScore

5.40

自引率

3.40%

发文量

170

审稿时长

3-8 weeks

期刊介绍： The European Journal of Clinical Pharmacology publishes original papers on all aspects of clinical pharmacology and drug therapy in humans. Manuscripts are welcomed on the following topics: therapeutic trials, pharmacokinetics/pharmacodynamics, pharmacogenetics, drug metabolism, adverse drug reactions, drug interactions, all aspects of drug development, development relating to teaching in clinical pharmacology, pharmacoepidemiology, and matters relating to the rational prescribing and safe use of drugs. Methodological contributions relevant to these topics are also welcomed. Data from animal experiments are accepted only in the context of original data in man reported in the same paper. EJCP will only consider manuscripts describing the frequency of allelic variants in different populations if this information is linked to functional data or new interesting variants. Highly relevant differences in frequency with a major impact in drug therapy for the respective population may be submitted as a letter to the editor. Straightforward phase I pharmacokinetic or pharmacodynamic studies as parts of new drug development will only be considered for publication if the paper involves -a compound that is interesting and new in some basic or fundamental way, or -methods that are original in some basic sense, or -a highly unexpected outcome, or -conclusions that are scientifically novel in some basic or fundamental sense.