Pre-existing Interstitial Lung Abnormalities and Immune Checkpoint Inhibitor-Related Pneumonitis in Solid Tumors: A Retrospective Analysis

Kohei Horiuchi; Shinnosuke Ikemura; Takashi Sato; Keitaro Shimozaki; Satoshi Okamori; Yoshitake Yamada; Yoichi Yokoyama; Masahiro Hashimoto; Masahiro Jinzaki; Ikuko Hirai; Takeru Funakoshi; Ryuichi Mizuno; Mototsugu Oya; Kenro Hirata; Yasuo Hamamoto; Hideki Terai; Hiroyuki Yasuda; Ichiro Kawada; Kenzo Soejima; Koichi Fukunaga

doi:10.1093/oncolo/oyad187

Pre-existing Interstitial Lung Abnormalities and Immune Checkpoint Inhibitor-Related Pneumonitis in Solid Tumors: A Retrospective Analysis

Oncologist. 2024 Jan 5;29(1):e108-e117. doi: 10.1093/oncolo/oyad187.

Authors

Kohei Horiuchi^{1

2}, Shinnosuke Ikemura^{1

3}, Takashi Sato^{1

4}, Keitaro Shimozaki⁵, Satoshi Okamori¹, Yoshitake Yamada⁶, Yoichi Yokoyama⁶, Masahiro Hashimoto⁶, Masahiro Jinzaki⁶, Ikuko Hirai⁷, Takeru Funakoshi⁷, Ryuichi Mizuno⁸, Mototsugu Oya⁸, Kenro Hirata^{3

5}, Yasuo Hamamoto^{3

5}, Hideki Terai¹, Hiroyuki Yasuda¹, Ichiro Kawada¹, Kenzo Soejima^{1

9}, Koichi Fukunaga¹

Affiliations

¹ Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan.
² Department of Medicine, Icahn School of Medicine at Mount Sinai, Mount Sinai Beth Israel, NY, USA.
³ Keio Cancer Center, Keio University School of Medicine, Tokyo, Japan.
⁴ Department of Respiratory Medicine, Kitasato University School of Medicine, Sagamihara, Japan.
⁵ Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
⁶ Department of Radiology, Keio University School of Medicine, Tokyo, Japan.
⁷ Department of Dermatology, Keio University School of Medicine, Tokyo, Japan.
⁸ Department of Urology, Keio University School of Medicine, Tokyo, Japan.
⁹ Clinical and Translational Research Center, Keio University School of Medicine, Tokyo, Japan.

Abstract

Background: Immune checkpoint inhibitors (ICIs) have demonstrated efficacy over previous cytotoxic chemotherapies in clinical trials among various tumors. Despite their favorable outcomes, they are associated with a unique set of toxicities termed as immune-related adverse events (irAEs). Among the toxicities, ICI-related pneumonitis has poor outcomes with little understanding of its risk factors. This retrospective study aimed to investigate whether pre-existing interstitial lung abnormality (ILA) is a potential risk factor for ICI-related pneumonitis.

Materials and methods: Patients with non-small cell lung cancer, malignant melanoma, renal cell carcinoma, and gastric cancer, who was administered either nivolumab, pembrolizumab, or atezolizumab between September 2014 and January 2019 were retrospectively reviewed. Information on baseline characteristics, computed tomography findings before administration of ICIs, clinical outcomes, and irAEs were collected from their medical records. Pre-existing ILA was categorized based on previous studies.

Results: Two-hundred-nine patients with a median age of 68 years were included and 23 (11.0%) developed ICI-related pneumonitis. While smoking history and ICI agents were associated with ICI-related pneumonitis (P = .005 and .044, respectively), the categories of ILA were not associated with ICI-related pneumonitis (P = .428). None of the features of lung abnormalities were also associated with ICI-related pneumonitis. Multivariate logistic analysis indicated that smoking history was the only significant predictor of ICI-related pneumonitis (P = .028).

Conclusion: This retrospective study did not demonstrate statistically significant association between pre-existing ILA and ICI-related pneumonitis, nor an association between radiologic features of ILA and ICI-related pneumonitis. Smoking history was independently associated with ICI-related pneumonitis. Further research is warranted for further understanding of the risk factors of ICI-related pneumonitis.

Keywords: gastric cancer; immune checkpoint inhibitor; interstitial lung disease; lung cancer; melanoma; renal cell carcinoma.

MeSH terms

Aged
Carcinoma, Non-Small-Cell Lung* / drug therapy
Humans
Immune Checkpoint Inhibitors / adverse effects
Kidney Neoplasms* / drug therapy
Lung / pathology
Lung Neoplasms* / pathology
Pneumonia* / chemically induced
Pneumonia* / diagnostic imaging
Retrospective Studies

Substances

Immune Checkpoint Inhibitors