Thoracic Cancer (Jul 2024)

Risk factors for severe immune‐related pneumonitis after nivolumab plus ipilimumab therapy for non‐small cell lung cancer

  • Toshiyuki Sumi,
  • Motoki Sekikawa,
  • Yuta Koshino,
  • Daiki Nagayama,
  • Yuta Nagahisa,
  • Keigo Matsuura,
  • Naoki Shijubou,
  • Koki Kamada,
  • Keito Suzuki,
  • Takumi Ikeda,
  • Haruhiko Michimata,
  • Hiroki Watanabe,
  • Yuichi Yamada,
  • Koichi Osuda,
  • Yusuke Tanaka,
  • Hirofumi Chiba

DOI
https://doi.org/10.1111/1759-7714.15385
Journal volume & issue
Vol. 15, no. 20
pp. 1572 – 1581

Abstract

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Abstract Background The efficacy of anti‐CTLA‐4 antibody (ipilimumab) plus anti‐programmed cell death 1 antibody (nivolumab) in treating advanced non‐small cell lung cancer (NSCLC) is impeded by an elevated risk of severe immune‐related adverse events. However, our understanding of associations among pre‐existing fibrosis, emphysematous changes, and objective indicators as predictive factors is limited for severe pneumonitis in NSCLC patients receiving this combination therapy. Thus, we retrospectively investigated these associations, including overall tumor burden, before treatment initiation in the Japanese population. Methods We focused on patients (n = 76) with pre‐existing interstitial lung disease (ILD) to identify predictors of severe pneumonitis. Variables included age, sex, smoking status, programmed cell death ligand 1 expression, overall tumor burden, chest computed tomography‐confirmed fibrosis, serum markers, and respiratory function test results. Results Severe pneumonitis was more frequent in patients with squamous cell carcinoma, fibrosis, low diffusing capacity for carbon monoxide (%DLCO), and high surfactant protein D (SP‐D) level. Notably, squamous cell carcinoma, baseline %DLCO, and SP‐D level were significant risk factors. Our findings revealed the nonsignificance of tumor burden (≥85 mm) in predicting severe pneumonitis, emphasizing the importance of pre‐existing ILD. Conversely, in cases without pre‐existing fibrosis, severe pneumonitis was not associated with %DLCO or SP‐D level (93.2% vs. 91.9%, and 63.3 vs. 40.9 ng/mL, respectively) and was more common in patients with a large overall tumor burden (97.5 vs. 70.0 mm). Conclusion Vigilant monitoring and early intervention are crucial for patients with squamous cell carcinoma, high SP‐D level, or low %DLCO undergoing ipilimumab plus nivolumab therapy.

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