B80-6-10 NSCLC Treatment Gone Rogue: Drug-Induced Pneumonitis in Just 14 Days of Lorlatinib

Introduction Immune checkpoint inhibitors, like lorlatinib, target malignant cells via the immune system, although they may disturb normal immunologic mechanisms and cause immune-related adverse events [1]. Immune checkpoint inhibitors, particularly lorlatinib, can cause drug-induced pneumonitis (DIP), with a median onset of 51 days, half of which occur within the first two months of treatment [1], [2]. Our case report describes lorlatinib, a third-generation anaplastic lymphoma kinase (ALK) inhibitor, as a causative agent of DIP with a rapid onset occurring within just two weeks of medication initiation. Case description A 63-year-old woman with stage IV ALK-positive NSCLC and recurrent malignant pleural effusions, status post right thoracentesis, presented with one day of worsening dyspnea two weeks after starting lorlatinib. She was hypoxic on room air, required BiPAP for respiratory distress, and had a chest tube placed for effusion drainage. She was admitted to the ICU for escalating oxygen needs and tachycardia. Respiratory PCR was positive for COVID-19, and she was treated with remdesivir, dexamethasone, and antibiotics for possible superimposed pneumonia. Repeat chest CT showed bilateral pneumonitis, more prominent on the left (Figure 1A), with marked improvement in tumor burden (Figure 1B).Given concern for DIP, lorlatinib therapy was held while inpatient, and the patient was switched from dexamethasone for COVID-19 infection to high-dose methylprednisolone therapy in an attempt to address the ongoing pneumonitis. The patient was discharged home with a follow-up scheduled with oncology for repeat chest CT imaging and consideration of alternative immunotherapy for NSCLC. Discussion Lorlatinib is an advanced targeted therapy that has transformed NSCLC management. This patient had received two weeks of lorlatinib without recent chest radiation. Pulmonary toxicity from lorlatinib is uncommon compared with other ALK or EGFR inhibitors, with drug-induced pneumonitis reported in fewer than 2% of trials [3].A concurrent COVID-19 infection was identified on respiratory PCR, though the patient lacked symptoms such as fever, cough, or sputum production. COVID pneumonitis typically shows bilateral, peripheral ground-glass opacities and consolidations [4], whereas drug-induced pneumonitis (DIP) often presents with more patchy or asymmetric infiltrates and variable patterns, including organizing pneumonia [5]. The patient’s bilateral, asymmetric, patchy inflammation was more consistent with DIP, especially given recent lorlatinib exposure. Clinical findings and imaging supported lorlatinib-associated pneumonitis over COVID-19 or radiation-induced causes. Conclusion With growing use of lorlatinib, clinicians should recognize ALK-inhibitor-induced pneumonitis and pursue prompt evaluation and management to reduce morbidity and mortality.