《JAMA Oncology》:免疫治疗疗效预测新方法

如今,免疫治疗已成为肿瘤治疗领域中的研究热点,虽然前景广阔,但是也存在着部分患者对免疫治疗不敏感,甚至无效的情况。近期,来自法国和西班牙的研究团队在著名医学杂志《JAMA Oncology》发表文章,探究了非小细胞肺癌免疫治疗疗效预测的指数,在精准治疗之路上又迈进了一步。




研究结果:在ICI治疗患者(466人)中,301名患者(65%)为男性,422(90%)如今或之前为吸烟者,401名患者(87%)体力状态等于或低于1;中位诊断年龄为62岁(范围29-86岁);270名患者(58%)患腺癌,159名患者(34%)患鳞癌。在129名有PD-L1数据的患者中,96名 (74%) PD-L1免疫组化染色至少1%,33名患者 (26%)为阴性。在测试集中,中位PFS和OS 分别为3个月 (95% CI, 2-4)和10个月(95% CI, 8-13)。dNLR值大于3并且LDH大于正常值上限时OS的独立预后因素(风险比 [HR] 2.22; 95% CI, 1.23-4.01 以及 HR, 2.51; 95% CI, 1.32-4.76)。LIPI提示预后差,中等和好的中位OS分别为3个月(95% CI, 1 个月- ), 10个月 (95% CI, 8 个月- ), 和34个月(95% CI, 17 个月- )。中位PFS分别为2.0 (95% CI, 1.7-4.0), 3.7 (95% CI, 3.0-4.8), 和6.3个月 (95% CI, 5.0-8.0) ( P < .001)。疾病控制率与dNLR值大于3并且LDH大于正常值上限也相关。这些结果在ICI验证集的OS,PFS和DCR中得到证实,但是在化疗组中无显著相关性。




 Derived neutrophils/(leukocytes minus neutrophils) ratio (dNLR) and lactate dehydrogenase (LDH) level have been correlated with immune checkpoint inhibitor (ICI) outcomes in patients with melanoma.

Design, Setting, and Participants  

Multicenter retrospective study with a test (n = 161) and a validation set (n = 305) treated with programmed death 1/programmed death ligand 1 (PD-1/PD-L1) inhibitors in 8 European centers, and a control cohort (n = 162) treated with chemotherapy only. Complete blood cell counts, LDH, and albumin levels were measured before ICI treatment. A lung immune prognostic index (LIPI) based on dNLR greater than 3 and LDH greater than upper limit of normal (ULN) was developed, characterizing 3 groups (good, 0 factors; intermediate, 1 factor; poor, 2 factors).

Main Outcomes and Measures  

The primary end point was overall survival (OS). Secondary end points were progression-free survival (PFS) and disease control rate (DCR).


In the pooled ICI cohort (N = 466), 301 patients (65%) were male, 422 (90%) were current or former smokers, and 401 (87%) had performance status of 1 or less; median age at diagnosis was 62 (range, 29-86) years; 270 (58%) had adenocarcinoma and 159 (34%) had squamous histologic subtype. Among 129 patients with PD-L1 data, 96 (74%) had PD-L1 of at least 1% by immunohistochemical analysis, and 33 (26%) had negative results. In the test cohort, median PFS and OS were 3 (95% CI, 2-4) and 10 (95% CI, 8-13) months, respectively. A dNLR greater than 3 and LDH greater than ULN were independently associated with OS (hazard ratio [HR] 2.22; 95% CI, 1.23-4.01 and HR, 2.51; 95% CI, 1.32-4.76, respectively). Median OS for poor, intermediate, and good LIPI was 3 months (95% CI, 1 month to not reached [NR]), 10 months (95% CI, 8 months to NR), and 34 months (95% CI, 17 months to NR), respectively, and median PFS was 2.0 (95% CI, 1.7-4.0), 3.7 (95% CI, 3.0-4.8), and 6.3 (95% CI, 5.0-8.0) months (both P < .001). Disease control rate was also correlated with dNLR greater than 3 and LDH greater than ULN. Results were reproducible in the ICI validation cohort for OS, PFS, and DCR, but were nonsignificant in the chemotherapy cohort.

Conclusions and Relevance  

Pretreatment LIPI, combining dNLR greater than 3 and LDH greater than ULN, was correlated with worse outcomes for ICI, but not for chemotherapy, suggesting that LIPI can serve as a potentially useful tool when selecting ICI treatment, raising the hypothesis that the LIPI might be useful for identifying patients unlikely to benefit from treatment with an ICI.




Reference: Association of the Lung Immune Prognostic Index With Immune Checkpoint Inhibitor Outcomes in Patients With Advanced Non–Small Cell Lung Cancer

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