BACKGROUND
Pembrolizumab prolongs survival in advanced esophageal cancer but carries a risk of checkpoint inhibitor pneumonitis (CIP), a rare and potentially fatal immune-related adverse event. Real-world management of CIP is particularly complex in developing countries, where endemic tuberculosis and limited access to advanced diagnostic tools for infection create substantial diagnostic uncertainty, especially in patients with pre-existing pulmonary comorbidities.
CASE REPORT
We report 3 cases of stage IV esophageal squamous cell carcinoma that developed pembrolizumab-related CIP with distinct clinical trajectories. Case 1 was a 51-year-old man with multiple metastases, grade 3 steroid-refractory CIP, rapid disease progression, transitioned to best supportive care. Case 2 was a 72-year-old man with COPD and cisplatin-induced renal failure and CIP difficult to distinguish from acute exacerbation, who fully recovered with corticosteroids, but pembrolizumab was permanently discontinued due to high recurrence risk. Case 3 was a 61-year-old previously healthy man, grade 2 CIP after 6 cycles, with complete recovery, and successful pembrolizumab rechallenge without relapse.
CONCLUSIONS
Three clinical scenarios provide a practical framework for managing checkpoint inhibitor pneumonitis (CIP): (1) palliation for severe, steroid-refractory CIP accompanied by oncological progression; (2) permanent discontinuation for steroid-responsive CIP in patients with high-risk baseline features; and (3) safe rechallenge for mild CIP following complete resolution. Key decision determinants include CIP severity, steroid responsiveness, underlying lung function, and anticipated therapeutic benefit. Empiric antibiotics should be individualized. This is a hypothesis-generating single-institution observation, not a validated management guideline.

Keywords: Esophageal Squamous Cell Carcinoma; Immunotherapy; Drug-Related Side Effects and Adverse Reactions; Secondary Prevention; Pulmonary Disease, Chronic Obstructive