肿瘤突变负荷应用于肺癌免疫治疗的专家共识

Expert Consensus on Tumor Mutational Burden for Immunotherapy in Lung Cancer

肺癌是全球范围内发病率和死亡率最高的恶性肿瘤之一。免疫检查点抑制剂(immune checkpoint inhibitors,ICIs),包括程序性死亡受体1(programmed cell death 1,PD-1)抗体、程序性死亡受体1配体(programmed cell death ligand 1,PD-L1)抗体和细胞毒性T淋巴细胞相关蛋白4(cytotoxic T lymphocyte antigen 4,CTLA-4)抗体,给部分晚期肺癌患者带来了显著的生存获益,改变了晚期肺癌的治疗格局。既往研究表明,PD-1/PD-L1抗体在晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)中的客观缓解率只有20%左右。所以临床亟需可靠的生物标志物协助筛选ICIs潜在获益人群,提高治疗响应率。肿瘤突变负荷(tumor mutational burden,TMB)是除PD-L1表达以外新兴的免疫治疗标志物。肺癌中PD-L1表达与TMB的相关性不大,评估TMB可扩大免疫治疗的获益人群。然而在临床实践中,TMB的检测、阈值的确定和临床指导策略仍然没有形成规范。本共识将对TMB检测和应用场景给出指导性建议,以促进TMB在肺癌免疫治疗中应用的规范化。

Lung cancer is one of the malignant tumors with the highest morbidity and mortality in the world.Immune checkpoint inhibitors(ICIs),including programmed cell death 1(PD-1)antibody,programmed cell death ligand 1(PD-L1)antibody,and cytotoxic T lymphocyte associated protein 4(CTLA-4)antibody.It has brought significant survival benefits to some patients with advanced lung cancer and changed the treatment pattern of advanced lung cancer.Previous studies have shown that the objective response rate of PD-1/PD-L1 antibody in advanced non-small cell lung cancer(NSCLC)is only about 20%.So reliable biomarkers are urgently needed to screen out the potential benefit population of ICIs and improve the clinical response rate.Tumor mutational burden(TMB)is an emerging biomarker of immunotherapy in addition to PD-L1 expression.There is little correlation between PD-L1 expression and TMB in lung cancer.It is estimated that TMB can expand the benefit population of immunotherapy.However,in clinical practice,the detection of TMB,the determination of cut-off value and the clinical guidance strategy are still not standardized.This consensus will give guiding suggestions on the detection and application scenarios of TMB,so as to promote the standardization of TMB application for immunotherapy in lung cancer.