Respiratory medicine · 2026
Impact of pre-existing interstitial lung abnormalities on pneumonitis risk and survival in chemo-naive patients with non-small-cell lung cancer receiving pembrolizumab plus chemotherapy.
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Machiyama Hirotomo, Matsumoto Kinnosuke, Shiroyama Takayuki, Miyazaki Akito, Komuta Kiyohide, Tamiya Motohiro, Tsukaguchi Akihiro, Tamiya Akihiro, Kinehara Yuhei, Moritomo Koki, Shoshihara Nao, Kuge Tomoki, Mihashi Yasuhiro, Mori Masahide, Yamauchi Keijiro, Suzuki Hidekazu, Kato Soichiro, Nishikawa Yuki, Niki Toshie, Azuma Koji, Osa Akio, Takeda Yoshito, Kumanogoh Atsushi
Аннотация
BACKGROUND: Pre-existing interstitial lung abnormalities (ILAs) are risk factors for immune checkpoint inhibitor related pneumonitis (ICI-P). However, the effects of first-line pembrolizumab plus platinum-based chemotherapy (PCT) on survival and ICI-P in chemo-naive patients with non-small cell lung cancer (NSCLC) and ILAs remain unclear. We, therefore, aimed to investigate these effects.
METHODS: We retrospectively analyzed patients with NSCLC who received first-line PCT at 12 Japanese institutions between December 2018 and December 2022. Based on computed tomography findings, patients were classified into non-ILA, non-subpleural (NS)-ILA, subpleural non-fibrotic (SNF)-ILA, or subpleural fibrotic (SF)-ILA. Overall survival (OS) and pneumonitis data were collected.
RESULTS: This study included 410 patients, comprising 307 without ILAs, 39 with NS-ILA, 47 with SNF-ILA, and 17 with SF-ILA. The cumulative incidences of any-grade ICI-P and grade ≥3 ICI-P differed among ILA subgroups (Gray's P < 0.001 and P = 0.008, respectively). In the multivariable analysis, SF-ILA was associated with higher cumulative incidences of any-grade pneumonitis (hazard ratio [HR], 4.75; 95% confidence interval [CI], 2.27-9.95; P < 0.001) and grade ≥3 pneumonitis (HR, 3.79; 95% CI, 1.43-10.1; P = 0.007) than non-ILA. Moreover, SF-ILA was an independent prognostic factor for OS (HR, 1.99; 95% CI, 1.06-3.73; P = 0.032). NS-ILA and SNF-ILA were not independently associated with an increased risk of death or severe pneumonitis compared with non-ILA.
CONCLUSIONS: ILA subtype assessment may enable risk stratification and inform treatment decisions for patients with NSCLC receiving PCT.
METHODS: We retrospectively analyzed patients with NSCLC who received first-line PCT at 12 Japanese institutions between December 2018 and December 2022. Based on computed tomography findings, patients were classified into non-ILA, non-subpleural (NS)-ILA, subpleural non-fibrotic (SNF)-ILA, or subpleural fibrotic (SF)-ILA. Overall survival (OS) and pneumonitis data were collected.
RESULTS: This study included 410 patients, comprising 307 without ILAs, 39 with NS-ILA, 47 with SNF-ILA, and 17 with SF-ILA. The cumulative incidences of any-grade ICI-P and grade ≥3 ICI-P differed among ILA subgroups (Gray's P < 0.001 and P = 0.008, respectively). In the multivariable analysis, SF-ILA was associated with higher cumulative incidences of any-grade pneumonitis (hazard ratio [HR], 4.75; 95% confidence interval [CI], 2.27-9.95; P < 0.001) and grade ≥3 pneumonitis (HR, 3.79; 95% CI, 1.43-10.1; P = 0.007) than non-ILA. Moreover, SF-ILA was an independent prognostic factor for OS (HR, 1.99; 95% CI, 1.06-3.73; P = 0.032). NS-ILA and SNF-ILA were not independently associated with an increased risk of death or severe pneumonitis compared with non-ILA.
CONCLUSIONS: ILA subtype assessment may enable risk stratification and inform treatment decisions for patients with NSCLC receiving PCT.