-Original-

Clinicopathological Characteristics of Everolimus-Associated Interstitial Lung Disease: A Single-Center Consecutive Analysis

Yoshinobu Saito¹, Yasuhiro Terasaki², Takeru Kashiwada¹, Toru Tanaka¹, Hiroyuki Takei³, Go Kimura⁴, Yukihiro Kondo⁴, Tetsuro Kawagoe⁵, Akira Matsushita⁶, Rintaro Noro¹, Yuji Minegishi¹, Koichiro Kamio¹, Masahiro Seike¹ and Akihiko Gemma¹

¹Department of Pulmonary Medicine and Oncology, Nippon Medical School, Tokyo, Japan
²Department of Analytic Human Pathology, Nippon Medical School, Tokyo, Japan
³Department of Breast Surgery and Oncology, Nippon Medical School, Tokyo, Japan
⁴Department of Urology, Nippon Medical School, Tokyo, Japan
⁵Department of Gastroenterology, Nippon Medical School, Tokyo, Japan
⁶Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Nippon Medical School, Tokyo, Japan

Background: Everolimus, a mammalian target of rapamycin inhibitor used as an antineoplastic drug, is associated with a remarkably high incidence of interstitial lung disease (ILD). The clinical and pathological characteristics of ILD caused by everolimus have not been thoroughly investigated; therefore, we aimed to elucidate the features of everolimus-associated ILD.
Methods: We retrospectively reviewed the medical records of patients who received everolimus for cancer treatment at our hospital. Patient backgrounds were compared between the ILD and non-ILD groups. Chest computed tomography (CT), changes in biomarkers, and lung histopathological features were analyzed for ILD cases.
Results: Sixty-six patients were reviewed, and ILD developed in 19. There were no differences in patient demographics between the ILD and non-ILD groups. The severity of ILD was grade 1 (G1) in 9 and grade 2 (G2) in 10 cases. Chest CT showed organizing pneumonia (OP) or a hypersensitive pneumonia pattern. The levels of lactate dehydrogenase, C-reactive protein, Krebs von den lungen-6, and surfactant protein-D (SP-D) at the onset of ILD were significantly higher than those at baseline. Analysis of G1 and G2 ILD subgroups showed a higher SP-D levels in the G2 subgroup. Five patients underwent lung biopsies; all specimens demonstrated alveolitis with lymphocytic infiltration and granulomatous lesions, and some had OP findings.
Conclusions: Everolimus-associated ILD is mild and has a favorable prognosis. Patients with symptomatic ILD were more likely to have higher SP-D levels than those with asymptomatic ILD. Granulomatous lesions are an important pathological feature of everolimus-associated ILD.

J Nippon Med Sch 2024; 91: 207-217

Keywords
everolimus, interstitial lung disease, KL-6, SP-D, granuloma

Correspondence to
Yoshinobu Saito, MD, PhD, Department of Pulmonary Medicine and Oncology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan
yo-saito@nms.ac.jp

Received, August 4, 2023
Accepted, November 22, 2023