Evaluation of the clinical characteristics of everolimus-induced lung injury and determination of associated risk factors.

Background: Everolimus (ERL), a mammalian target of rapamycin (mTOR) inhibitor, has been used for the management of several advanced cancers. ERL frequently causes lung injury, although the clinical and radiographic features have not been clarified. The aim of this study was to assess the clinical features of ERL-induced lung injury and determine the associated risk factors.

Methods: This single-center, retrospective study included 45 patients (29 men, 16 women; age, 12-78 years) who had received ERL at our hospital between August 2010 and March 2016. Drug-induced lung injury (DILI) was diagnosed using the Japanese Respiratory Society criteria. We obtained information regarding the clinical course, symptoms, clinical findings, blood test findings, and chest computed tomography findings from the patients' medical records. Risk factors for DILI onset were investigated using the Wilcoxon rank sum test.

Results: Fifteen patients (33%) were diagnosed with DILI. The median time from ERL administration to DILI onset was 64 days. High Serum Krebs von den Lungen-6 (KL-6) levels and a low estimated glomerular filtration rate (eGFR) before ERL administration were found to be significant risk factors for DILI. KL-6 and lactate dehydrogenase (LDH) were significantly elevated at the onset of DILI. All 15 patients recovered; 11 were without steroids.

Conclusions: Our results suggest that patients with high KL-6 levels and a low eGFR at baseline are at increased risk of ERL-induced lung injury. In addition, KL-6 and LDH may be useful biomarkers of ERL-induced lung injury.