Pre-Treatment Peripheral Blood Parameters as Prognostic Biomarkers in Cancer Patients Receiving Immune Checkpoint Inhibitors.

Danielle Bernardo, Nirosha J Murugan, Ioannis A Voutsadakis
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Abstract

Background: Immune checkpoint inhibitors have significantly improved outcomes in select cancers; however, not all patients respond to these therapies, and the duration of the response varies among responders. Markers predictive of the response to immunotherapy, such as PD-L1 expression determined by immunohistochemical staining of tumor sections and microsatellite status, have been identified. Some of these are used in companion diagnostics approved for clinical practice. Additional easy-to-use biomarkers may help clinicians to predict the efficacy of these drugs in individual patients. Materials and Methods: A retrospective review of the medical records of patients with metastatic cancer treated with immune checkpoint inhibitors in our cancer center was performed to identify the clinical and hematologic parameters associated with survival outcomes. Results: Among the 163 patients included in the study, most had lung cancer, followed by kidney cancer, melanoma, and bladder cancer. Most patients (61.3%) were male and had good performance status. Nivolumab and pembrolizumab were immune checkpoint inhibitors utilized in 85.9% of cases. Age, sex, and primary cancer type were not associated with survival outcomes. Among the peripheral blood parameters evaluated, lymphocytopenia was the strongest predictor of adverse survival outcomes in univariate analysis and the only clinical or hematologic biomarker that retained significance for overall survival (OS) prediction in multivariate analysis. Conclusion: Among the clinical and hematologic parameters routinely used in the clinic, a lymphocyte count below 1 x 109/ L was predictive of adverse OS in patients with metastatic cancers receiving immune checkpoint inhibitors.

治疗前外周血参数作为接受免疫检查点抑制剂的癌症患者的预后生物标志物
背景:免疫检查点抑制剂可显著改善特定癌症的预后;然而,并非所有患者都对这些疗法有反应,反应的持续时间因反应者而异。已经确定了预测免疫治疗反应的标志物,例如通过肿瘤切片的免疫组织化学染色和微卫星状态确定的PD-L1表达。其中一些用于临床实践批准的伴随诊断。其他易于使用的生物标志物可以帮助临床医生预测这些药物对个体患者的疗效。材料和方法:对我们癌症中心接受免疫检查点抑制剂治疗的转移性癌症患者的医疗记录进行回顾性审查,以确定与生存结果相关的临床和血液学参数。结果:在纳入研究的163例患者中,大多数患有肺癌,其次是肾癌、黑色素瘤和膀胱癌。患者以男性居多(61.3%),运动状态良好。85.9%的病例使用Nivolumab和pembrolizumab作为免疫检查点抑制剂。年龄、性别和原发癌症类型与生存结果无关。在评估的外周血参数中,淋巴细胞减少是单变量分析中不良生存结果的最强预测因子,也是唯一在多变量分析中保留总生存(OS)预测意义的临床或血液学生物标志物。结论:在临床常规使用的临床和血液学参数中,淋巴细胞计数低于1 × 109/ L可预测接受免疫检查点抑制剂的转移性癌症患者的不良OS。
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