[Autoimmune pulmonary alveolar proteinosis induced by brigatinib: a case report and literature review].

Objective: To investigate the clinical features, diagnostic and therapeutic considerations, and outcomes of pulmonary alveolar proteinosis (PAP) induced by tyrosine kinase inhibitor (TKI), aiming to enhance clinicians' understanding of this rare form of interstitial lung disease associated with TKI. Methods: This was a case series study. One case of autoimmune PAP induced by brigatinib from the Department of Respiratory and Critical Care Medicine, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, was collected. A literature search of the Wanfang Database, China National Knowledge Infrastructure (CNKI), and PubMed up to October 31, 2025, identified an additional four cases of TKI-induced PAP. A total of five cases were included. The baseline clinical characteristics, imaging findings, pathological results, treatments, and clinical outcomes of these five patients were summarized and analyzed. Results: Among the five patients, one was male and four were female. The median time from TKIs initiation to PAP onset was 5 months (range: 1.3-21 months). Underlying diseases included lung cancer (2 cases) and hematologic malignancies (3 cases). Three patients were treated with imatinib (one later switched to nilotinib and then dasatinib), while one patient each received osimertinib and brigatinib. Serum KL-6 levels were significantly elevated in four patients. Anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) antibody levels were elevated in the serum of three patients, with one also showing increased GM-CSF levels in bronchoalveolar lavage fluid (BALF). Chest imaging revealed bilateral ground-glass opacities in two cases, bilateral patchy infiltrates in one case, and the typical "crazy-paving pattern" in two cases. The diagnosis of PAP was confirmed in all five patients via BALF cytology and/or lung tissue histopathology. Treatment for PAP consisted of no specific therapy in two patients, whole lung lavage (WLL) in two, and inhaled GM-CSF in one. Regarding clinical outcomes, one patient died of respiratory failure, one died of primary disease progression after switching TKI, two showed symptomatic improvement with stable disease, and one had a favorable prognosis. Conclusions: Autoimmune PAP is a rare pulmonary complication associated with TKI. When interstitial pneumonia occurs during TKI administration and does not respond to drug withdrawal and corticosteroid treatment, careful analysis of chest imaging features, along with bronchoalveolar lavage and/or bronchoscopic lung biopsy, is necessary for a definitive diagnosis. This case series and literature review suggest that nebulized GM-CSF or whole lung lavage (WLL) may be effective treatment options for TKI-induced autoimmune PAP.