Association of interstitial lung abnormalities with cytotoxic agent-induced pneumonitis in patients with malignancy

Kyohei Oishi; Hironao Hozumi; Nobuko Yoshizawa; Shintaro Ichikawa; Yusuke Inoue; Hideki Yasui; Yuzo Suzuki; Masato Karayama; Kazuki Furuhashi; Noriyuki Enomoto; Tomoyuki Fujisawa; Satoshi Goshima; Naoki Inui; Takafumi Suda

doi:10.1016/j.rmed.2024.107924

Association of interstitial lung abnormalities with cytotoxic agent-induced pneumonitis in patients with malignancy

Respir Med. 2024 Dec 27:237:107924. doi: 10.1016/j.rmed.2024.107924. Online ahead of print.

Affiliations

¹ Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama Chuoku, Hamamatsu, 431-3192, Japan.
² Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama Chuoku, Hamamatsu, 431-3192, Japan. Electronic address: hozumi@hama-med.ac.jp.
³ Department of Radiology, Hamamatsu University School of Medicine, 1-20-1 Handayama Chuoku, Hamamatsu, 431-3192, Japan.
⁴ Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama Chuoku, Hamamatsu, 431-3192, Japan; Department of Clinical Pharmacology and Therapeutics, Hamamatsu University School of Medicine, 1-20-1 Handayama Chuoku, Hamamatsu, 431-3192, Japan.

PMID: 39733813
DOI: 10.1016/j.rmed.2024.107924

Abstract

Background and objective: The association between interstitial lung abnormalities (ILA) and various conditions and diseases, including drug-related pneumonitis (DRP), has been reported. However, the association of the presence of ILA with developing DRP in patients undergoing cytotoxic agent-based chemotherapy, one of the standard treatments for malignancies, remains unclear. This warrants urgent investigation.

Methods: We included consecutive patients diagnosed with malignancy and treated with cytotoxic agents with/without immune checkpoint inhibitors (ICIs). We used Gray's method and multivariate Fine-Gray sub-distribution hazards analysis to evaluate the cumulative incidence of DRP (common terminology criteria for adverse events grade of ≥3) and the association between ILA and DRP development, respectively.

Results: Among 786 patients, 58 (7.3 %) demonstrated ILA. Patients with ILA were older, predominantly male, and reported a higher smoking history compared to those without ILA. The 90-day cumulative incidence of cytotoxic agent-induced DRP with/without ICIs was significantly higher in patients with ILA than in those without ILA (6.0 % vs. 1.2 %, p = 0.006). Multivariate analysis, adjusted for age, sex, and smoking history, revealed that ILA was associated with an increased risk of developing DRP due to cytotoxic agents with/without ICIs (hazard ratio [HR] 3.11, 95 % confidence interval [CI]: 1.06-9.14, p = 0.039) and cytotoxic agents alone (HR: 5.53, 95 % CI: 1.55-19.7, p = 0.008).

Conclusions: The presence of ILA is associated with an increased risk of developing DRP in patients undergoing cytotoxic agent-based chemotherapy. Therefore, evaluating the presence of ILA before determining chemotherapy regimens that include cytotoxic agents is recommended.

Keywords: Drug-induced pneumonia; Drug-related pneumonitis; Interstitial lung abnormalities.