Department of Integrated Therapy, Fudan University Shanghai Cancer Center, Shanghai Medical College, Shanghai, China.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
Respir Res. 2024 Jun 21;25(1):253. doi: 10.1186/s12931-024-02885-0.
There is a desperate for the identification of more accurate and efficient biomarkers for ICI responses in patients with SCLC.
The data of our study was obtained from IMpower133 study. A total of 202 patients with SCLC received the treatment of placebo plus carboplatin plus etoposide (EC) while a total of 201 patients with SCLC received the treatment of atezolizumab plus EC. Overall survival (OS) was compared using Kaplan Meier analyses. Univariate and multivariate Cox regression analysis were used to determine independent prognostic variables affecting OS in patients with SCLC.
We have demonstrated that a higher TMB adjusted by a lower neutrophil-to-lymphocyte ratio (NLR) is significantly correlated with improved OS, in patients with SCLC subject to either atezolizumab or placebo (P = 0.001 for atezolizumab and P = 0.034 for placebo). Moreover, Cox model showed that TMB < 10 mut/Mb adjusted by NLR ≥ median was an independent factor of OS for atezolizumab-treated SCLC patients (hazard ratio [HR], 2.82; 95% confidence interval; 1.52-5.24; P = 0.001). Both univariate and multivariate cox regression analysis showed that for patients with SCLC harboring low NLR and high TMB, survival is significantly longer in those treated with atezolizumab than those treated with placebo. Survival benefit is significantly higher in atezolizumab-treated patients with SCLC than those treated with placebo (P = 0.018 for TMB cutoff = 10 mut/Mb, P = 0.034 for TMB cutoff = 16 mut/Mb).
Our findings provide a promising insight into the utility of NLR-adjusted TMB in the prognosis and immune responses in patients with SCLC.
目前迫切需要鉴定更准确、更有效的免疫检查点抑制剂（ICI）反应生物标志物，以用于小细胞肺癌（SCLC）患者。
本研究数据来自 IMpower133 研究。共 202 例 SCLC 患者接受安慰剂联合卡铂加依托泊苷（EC）治疗，201 例 SCLC 患者接受阿替利珠单抗联合 EC 治疗。采用 Kaplan-Meier 分析比较总生存期（OS）。采用单因素和多因素 Cox 回归分析确定影响 SCLC 患者 OS 的独立预后因素。
我们发现，SCLC 患者中，经中性粒细胞与淋巴细胞比值（NLR）校正后的较高肿瘤突变负荷（TMB）与 OS 改善显著相关，无论是接受阿替利珠单抗还是安慰剂治疗的患者均如此（阿替利珠单抗组 P=0.001，安慰剂组 P=0.034）。此外，Cox 模型显示，经 NLR 校正后的 TMB<10 mut/Mb 且 NLR≥中位数是阿替利珠单抗治疗 SCLC 患者 OS 的独立因素（风险比[HR]，2.82；95%置信区间，1.52-5.24；P=0.001）。单因素和多因素 Cox 回归分析均显示，对于 NLR 较低、TMB 较高的 SCLC 患者，阿替利珠单抗治疗组的生存时间明显长于安慰剂治疗组。阿替利珠单抗治疗组的生存获益明显高于安慰剂治疗组（TMB 截止值为 10 mut/Mb 时 P=0.018，TMB 截止值为 16 mut/Mb 时 P=0.034）。
本研究结果为 NLR 校正的 TMB 在 SCLC 患者预后和免疫反应中的应用提供了有前景的见解。
Zotero 插件
