Department of Respiratory Medicine, Respiratory Disease Center, Seirei Mikatahara General Hospital, 3453, Mikatahara, Kitaku, Hamamatsu, Shizuoka, 433-8558, Japan.
Department of Internal Medicine III, Wakayama Medical University, Wakayama, Japan.
Med Oncol. 2019 Mar 1;36(4):33. doi: 10.1007/s12032-019-1255-3.
Early elevation of inflammatory cytokines, such as IL-6 or TNF-α, or CRP, which is a surrogate marker for IL-6, following commencement of PD-1/L1 inhibitors (PD1-I) may represent early activation of immune-cells. Serum IL-6 and TNF-α were measured in 10 non-small cell lung cancer patients who were evaluable within the 7 days before and after commencement of PD1-I. For CRP, medical records were reviewed and 34 patients with measured CRP within the 7 days before and after the treatment were evaluated. In the 10 patients analyzed for IL-6/TNF-α, the serum levels of IL-6/TNF-α were not significantly different between pre- and post-initial PD1-I [IL-6 20.3 (2.6-49.9) and 22.9 (3.6-96.1) pg/mL, p = 0.453; TNF-α 1.6 (0.7-6.3) and 3.3 (0.7-9.6) pg/mL, p = 0.329]; however, all four responses were observed among the 7 IL-6-elevated cases, resulting in a response rate of 57%. In the 34 patients analyzed for CRP, CRP was significantly increased after initial PD1-I [1.8 (0.1-17.8) mg/dL, 2.4 (0.0-27.8), p = 0.001]. Notably, in the 31 evaluable cases, all responses were again observed in either the IL-6 or CRP elevated groups and the response rate was 46% (11 of 24). The median overall survival time was not reached in the elevated group and was 112 days in the non-elevated group (p = 0.069). The early increase in inflammatory cytokines with PD1-I was indicated to be predictive for the efficacy in patients with non-small cell lung cancer.
PD-1/L1 抑制剂（PD1-I）开始使用后，炎症细胞因子（如 IL-6 或 TNF-α）或 CRP（IL-6 的替代标志物）的早期升高可能代表免疫细胞的早期激活。在可评估的 10 例非小细胞肺癌患者中，在 PD1-I 开始前和开始后 7 天内测量了血清 IL-6 和 TNF-α。对于 CRP，回顾了病历，并评估了治疗前和治疗后 7 天内测量了 CRP 的 34 例患者。在分析的 10 例 IL-6/TNF-α 患者中，IL-6/TNF-α 的血清水平在初始 PD1-I 前后无显著差异[IL-6 20.3（2.6-49.9）和 22.9（3.6-96.1）pg/mL，p=0.453；TNF-α 1.6（0.7-6.3）和 3.3（0.7-9.6）pg/mL，p=0.329]；然而，所有 4 例反应均在 7 例 IL-6 升高的病例中观察到，反应率为 57%。在分析 CRP 的 34 例患者中，初始 PD1-I 后 CRP 显著升高[1.8（0.1-17.8）mg/dL，2.4（0.0-27.8），p=0.001]。值得注意的是，在 31 例可评估的病例中，所有反应均在 IL-6 或 CRP 升高的组中再次观察到，反应率为 46%（24 例中有 11 例）。升高组的中位总生存时间未达到，非升高组为 112 天（p=0.069）。PD1-I 后炎症细胞因子的早期增加表明对非小细胞肺癌患者的疗效具有预测性。
