Supplementary Material for: Almonertinib-Induced Interstitial Lung Disease in an NSCLC Patient Harboring EGFR Ex19del Mutation: A Case Report

Introduction: Almonertinib, a third-generation epidermal growth factor receptor–tyrosine kinase inhibitor, has demonstrated favorable clinical efficacy in the treatment of non-small cell lung cancer and is recommended as a first-line treatment for patients with EGFR-sensitive mutations. Although it rarely induces interstitial lung disease (ILD), we report a case of a stage IVB EGFR Ex19del mutation in an older female adult with almonertinib-induced grade III ILD. Case Presentation: A 55-year-old Asian woman diagnosed with stage IVB lung adenocarcinoma (cT4N3M1c per the AJCC 8th edition) presented with extensive metastases involving the right hilar, mediastinal, bilateral cervical, retroperitoneal lymph nodes, bilateral adrenal glands, brain, and bone. Following the detection of an EGFR Ex19del mutation, she was initiated on almonertinib treatment. Notably, progressive respiratory deterioration developed 3 months post-treatment, characterized by dyspnea, hypoxemia, and interstitial lung changes on high-resolution computed tomography. ILD diagnosis was confirmed through multidisciplinary consensus. Immediate discontinuation of almonertinib combined with intravenous methylprednisolone resulted in significant clinical and radiological improvement within 7 days. Conclusion: This case highlights two important clinical implications: (1) almonertinib-associated ILD can rapidly progress to a life-threatening condition; and (2) occupational inhalational exposures (e.g., dust and smoking) have been directly and indirectly implicated as potential risk factors for EGFR-TKI–induced pulmonary toxicity in prior studies and may have contributed to the outcome in this case. Clinicians should maintain heightened vigilance for respiratory complications during almonertinib therapy, particularly in patients with pre-existing pulmonary risk factors.