Data_Sheet_1_Systematic Assessment of Risk of Fever in Solid Tumor Patients Treated With PD-1/PD-L1 Inhibitors: A Systematic Review and Meta-Analysis.zip

Purpose: Drug-induced fever is frequently reported in cancer patients treated with anti-programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1), and stoppage of the offending agent is the management of choice. However, given the complex management of cancer patients, this needs to be carefully studied. Therefore, we conducted a meta-analysis to estimate the risk of fever associated with anti-PD-1/PD-L1 in cancer patients.Methods: From May 2010 to 2020, an electronic search was conducted through PubMed for relevant studies. All clinical trials reporting fever in cancer patients treated with PD-1/PD-L1 inhibitors were included, while other designs were excluded. A manual search was also conducted to search for relevant articles. Outcomes included the risk of pyrexia and febrile neutropenia in the overall population and based on the grade of fever (all grades vs. grades 3–5). The Newcastle–Ottawa Scale was used to assess the quality of included studies.Results: Thirty-one articles, involving 27 clinical trials and 15,867 participants, were included. The increased risk of pyrexia for all grades is only found when PD-1/PD-L1 plus cytotoxic T lymphocyte-associated protein 4 (CTLA-4) was compared to CTLA-4 [odds ratio (OR) = 2.48, 95% CI: 1.17, 5.23]. The risk of febrile neutropenia for all-grade fever was significantly lower in the PD-1/PD-L1 group compared to that of chemotherapy alone (OR = 0.02, 95% CI: 0.01, 0.05). A similar trend in the risk of febrile neutropenia was also found for grades 3–5 (OR = 0.02, 95% CI: 0.01, 0.05).Conclusion: The increased risk of pyrexia for all grades could only be found when PD-1/PD-L1 plus CTLA-4 was compared with CTLA-4. Meanwhile, compared to chemotherapy, PD-1/PD-L1 inhibitors reduced the risk of febrile neutropenia.

目的：在采用抗程序性细胞死亡1（PD-1）/程序性细胞死亡配体1（PD-L1）治疗的癌症患者中，药物诱导的发热现象屡见不鲜，终止致热药物是首选的治疗方法。然而，鉴于癌症患者的复杂管理状况，这一问题亟待深入探究。因此，本研究通过对相关文献进行荟萃分析，旨在评估抗PD-1/PD-L1与癌症患者发热风险的相关性。方法：自2010年5月至2020年，通过PubMed数据库进行电子检索，收集所有报告PD-1/PD-L1抑制剂治疗癌症患者发热的临床试验。排除其他类型的研究设计。此外，还进行了人工检索以查找相关文献。研究结果包括总体人群中发热和发热性中性粒细胞减少症的风险，以及根据发热程度（所有等级 vs. 3-5级）的风险。采用纽卡斯尔-渥太华量表（Newcastle–Ottawa Scale）对纳入研究的质量进行评估。结果：纳入31篇文章，涉及27项临床试验和15,867名参与者。仅在PD-1/PD-L1联合细胞毒性T淋巴细胞相关蛋白4（CTLA-4）与单独使用CTLA-4进行比较时，才发现了所有等级发热风险的显著增加[比值比（OR）= 2.48，95% CI：1.17，5.23]。与单独化疗相比，PD-1/PD-L1组中所有等级发热的发热性中性粒细胞减少症风险显著降低（OR = 0.02，95% CI：0.01，0.05）。对于3-5级发热，发热性中性粒细胞减少症风险的趋势与上述结果相似（OR = 0.02，95% CI：0.01，0.05）。结论：仅在PD-1/PD-L1联合CTLA-4与单独使用CTLA-4进行比较时，才观察到所有等级发热风险的升高。同时，与化疗相比，PD-1/PD-L1抑制剂降低了发热性中性粒细胞减少症的风险。