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Background <p>Immune checkpoint inhibitors (ICIs) offer durable progression-free survival (PFS) benefit in a subset of patients with advanced non-small cell lung cancer (NSCLC). However, the predictors of long-term PFS (LTPFS) remain unclear.</p> Methods <p>Advanced NSCLC patients receiving first-line ICIs monotherapy at Guangdong Lung Cancer Institute between December 2017 and August 2022 were identified. Predictive value of different characteristics was evaluated in LTPFS (PFS ≥ 24&#xa0;months) compared with short-term PFS (STPFS, PFS ≤ 3&#xa0;months). Circulating cytokine levels were evaluated in paired peripheral blood samples collected before and after ICIs treatment.</p> Results <p>Among 202 patients identified and 171 included (median follow-up: 41.0&#xa0;months), 44 (25.7%) experienced LTPFS, associated with a 5-year overall survival (OS) rate of 81.2%. Squamous NSCLC, intermediate or poor lung immune prognostic index (LIPI) score, and liver metastases, were negatively associated with LTPFS. High tumor mutational burden (TMB, ≥ 10 mutations/megabase) was enriched in LTPFS compared to STPFS (<i>P</i> = 0.002). Patients with both high TMB and PD-L1 demonstrated the greatest survival benefit from first-line ICIs monotherapy (median PFS: 24.5&#xa0;months, median OS: 67.0&#xa0;months). Thirty-eight peripheral blood samples were collected before and after ICIs treatment from 10 patients with LTPFS and 9 with STPFS, which revealed increased CCL11 (<i>P</i> = 0.013) and decreased IL1RA (<i>P</i> = 0.001) and IL17A (<i>P</i> = 0.003) levels in LTPFS after ICIs treatment.</p> Conclusion <p>Distinct clinical characteristics, including TMB, PD-L1, pathologic subtypes, LIPI score, number of organs involved, metastatic sites, and dynamic circulating cytokines profile features, can distinguish NSCLC patients achieving LTPFS from those with STPFS following first-line ICIs monotherapy.</p>

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Clinical and dynamic circulating cytokines profile features of long-term progression-free survival benefit to immune checkpoint inhibitors in advanced non–small cell lung cancer

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年4月17日

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  • Jia-Yi Deng,
  • Ming Gao,
  • Xue Fan,
  • Hong-Hong Yan,
  • Wei-Chi Luo,
  • Ming-Yi Yang,
  • Xiao-Rong Yang,
  • Zhi-Hong Chen,
  • Chong-Rui Xu,
  • Qing Zhou

摘要

Background

Immune checkpoint inhibitors (ICIs) offer durable progression-free survival (PFS) benefit in a subset of patients with advanced non-small cell lung cancer (NSCLC). However, the predictors of long-term PFS (LTPFS) remain unclear.

Methods

Advanced NSCLC patients receiving first-line ICIs monotherapy at Guangdong Lung Cancer Institute between December 2017 and August 2022 were identified. Predictive value of different characteristics was evaluated in LTPFS (PFS ≥ 24 months) compared with short-term PFS (STPFS, PFS ≤ 3 months). Circulating cytokine levels were evaluated in paired peripheral blood samples collected before and after ICIs treatment.

Results

Among 202 patients identified and 171 included (median follow-up: 41.0 months), 44 (25.7%) experienced LTPFS, associated with a 5-year overall survival (OS) rate of 81.2%. Squamous NSCLC, intermediate or poor lung immune prognostic index (LIPI) score, and liver metastases, were negatively associated with LTPFS. High tumor mutational burden (TMB, ≥ 10 mutations/megabase) was enriched in LTPFS compared to STPFS (P = 0.002). Patients with both high TMB and PD-L1 demonstrated the greatest survival benefit from first-line ICIs monotherapy (median PFS: 24.5 months, median OS: 67.0 months). Thirty-eight peripheral blood samples were collected before and after ICIs treatment from 10 patients with LTPFS and 9 with STPFS, which revealed increased CCL11 (P = 0.013) and decreased IL1RA (P = 0.001) and IL17A (P = 0.003) levels in LTPFS after ICIs treatment.

Conclusion

Distinct clinical characteristics, including TMB, PD-L1, pathologic subtypes, LIPI score, number of organs involved, metastatic sites, and dynamic circulating cytokines profile features, can distinguish NSCLC patients achieving LTPFS from those with STPFS following first-line ICIs monotherapy.