BMC Medicine (Jan 2023)

Interstitial pneumonitis associated with combined regimen of immunotherapy and conventional therapies—pharmacovigilance database analysis with real-world data validation

  • Xue-Jun Guo,
  • Xiao-Ting Cai,
  • Zi-Xuan Rong,
  • Yan-Pei Zhang,
  • Yu-Xiang Wen,
  • Xue Bai,
  • Jian Wang,
  • Qiang John Fu,
  • Ze-Qin Guo,
  • Li-Li Long,
  • Si-Cong Ma,
  • Xin-Ran Tang,
  • Li Liu,
  • Jian Guan,
  • Zhong-Yi Dong,
  • De-Hua Wu

DOI
https://doi.org/10.1186/s12916-022-02713-6
Journal volume & issue
Vol. 21, no. 1
pp. 1 – 12

Abstract

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Abstract Background Immune checkpoint inhibitor (ICI) therapy combined with conventional therapies is being broadly applied in non-small cell lung cancer (NSCLC) patients. However, the risk of interstitial pneumonitis (IP) following a combined regimen is incompletely characterized. Methods A total of 46,127 NSCLC patients were extracted for disproportionality analyses of IP from the Food and Drug Administration’s Adverse Event Reporting System (FAERS) database. A total of 1108 NSCLC patients who received ICI treatment at Nanfang Hospital of Southern Medical University were collected and utilized for real-world validation. Results Of the 46,127 patients with NSCLC, 3830 cases (8.3%; 95% confidence interval [CI], 8.05–8.56) developed IP. Multivariable logistic regression analyses revealed that the adjusted ROR of ICI combined with radiation (RT) was the highest (121.69; 95% CI, 83.60–184.96; P < 0.0001) among all therapies, while that of ICI combined with chemotherapy (CHEMO) or targeted therapy (TARGET) was 0.90 (95% CI, 0.78–1.04; P = 0.160) and 1.49 (95% CI, 0.95–2.23; P = 0.065), respectively, using ICI monotherapy as reference. Furthermore, analyses from our validation cohort of 1108 cases showed that the adjusted odds ratio of ICI combined with RT was the highest (12.25; 95% CI, 3.34–50.22; P < 0.01) among all the therapies, while that of ICI combined with CHEMO or TARGET was 2.32 (95% CI, 0.89–7.92; P = 0.12) and 0.66 (95% CI, 0.03–4.55; P = 0.71), respectively, using ICI monotherapy as reference. Conclusions Compared with ICI monotherapy, ICI combined with RT, rather than with CHEMO or TARGET, is associated with a higher risk of IP in NSCLC patients. Hence, patients receiving these treatments should be carefully monitored for IP.

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