Akhmedov Mobil, Zeynalova Pervin, Fedenko Alexander, Kaprin Andrey
P.A. Hertsen Moscow Oncology Research Institute, branch of the National Medical Radiology Research Center, Moscow, Russian Federation.
Department of Oncology and Oncosurgery, Russian University of Medicine, Moscow, Russian Federation.
Invest New Drugs. 2025 Jul 21. doi: 10.1007/s10637-025-01565-0.
No correlation between the dose, adverse events, and efficacy was detected in clinical trials of anti-PD-1 antibodies across a range of solid and hematological malignancies. Given that dose reduction with potentially comparable clinical efficacy may improve access to treatment, particularly in low-income regions, we conducted a systematic review and meta-analysis to evaluate the efficacy and safety of low-dose PD-1 inhibitor monotherapy in relapsed/refractory (r/r) classic Hodgkin lymphoma (cHL).
Relevant reports were identified through PUBMED, MEDLINE, Cochrane, ScienceDirect databases, and major international conference proceedings, from inception till December 1, 2024. The risk of bias was assessed independently by two authors using the Joanna Briggs's critical appraisal checklist for studies reporting prevalence data. Heterogeneity was assessed using Cochran's Q test, with statistical significance defined as p < 0.05; I statistic was used to quantify heterogeneity. Random effects models (Der-Simonian method) was used to pool results from primary studies in the presence of significant heterogeneity.
After screening, 13 reports including 148 patients were included in the systematic review. After exclusion of duplicated reports, studies with less than 5 patients, and studies with unextractable data, five studies with a total of 84 patients were included in the meta-analysis. The pooled objective response rate (ORR) with low-dose PD-1 inhibition in r/r cHL, as determined by meta-analysis, was 87% (95% CI, 71.9%-100%), with a corresponding complete response (CR) rate of 53.9% (95% CI, 34.7%-73.1%). The ORR with low-dose nivolumab was 83.8% (95% CI, 64.2%-100%), with a CR rate of 43.3% (95% CI, 29.7%-56.9%). The pooled rate of any-grade adverse events after low-dose PD-1 inhibition was 55.7% (95% CI, 36.1%-75.3%), with a grade 3-4 adverse event rate of 7.5% (95% CI, 1.7%-13.3%).
This systematic review and meta-analysis demonstrated the high efficacy and acceptable toxicity of low-dose PD-1 inhibition in r/r cHL.
在一系列实体瘤和血液系统恶性肿瘤的抗PD-1抗体临床试验中，未检测到剂量、不良事件和疗效之间的相关性。鉴于降低剂量且临床疗效可能相当，这可能会改善治疗的可及性，尤其是在低收入地区，我们进行了一项系统评价和荟萃分析，以评估低剂量PD-1抑制剂单药治疗复发/难治性（r/r）经典霍奇金淋巴瘤（cHL）的疗效和安全性。
通过PUBMED、MEDLINE、Cochrane、ScienceDirect数据库以及主要国际会议论文集，检索从创刊至2024年12月1日的相关报告。由两位作者使用乔安娜·布里格斯研究所报告患病率数据研究的关键评估清单，独立评估偏倚风险。使用Cochran's Q检验评估异质性，统计学显著性定义为p < 0.05；I统计量用于量化异质性。在存在显著异质性的情况下，采用随机效应模型（Der-Simonian方法）汇总主要研究的结果。
筛选后，13份报告（包括148例患者）纳入系统评价。排除重复报告、患者少于5例的研究以及数据不可提取的研究后，5项研究（共84例患者）纳入荟萃分析。荟萃分析确定，r/r cHL中低剂量PD-1抑制的汇总客观缓解率（ORR）为87%（95%CI，71.9%-100%），相应的完全缓解（CR）率为53.9%（95%CI，34.7%-73.1%）。低剂量纳武利尤单抗的ORR为83.8%（95%CI，64.2%-100%），CR率为43.3%（95%CI，29.7%-56.9%）。低剂量PD-1抑制后任何级别的不良事件汇总发生率为55.7%（95%CI，36.1%-75.3%），3-4级不良事件发生率为7.5%（95%CI，1.7%-13.3%）。
这项系统评价和荟萃分析表明，低剂量PD-1抑制在r/r cHL中具有高疗效和可接受的毒性。
