Successful rechallenge of immune checkpoint inhibitors after severe immune-related hepatitis, thyroiditis and hypophysitis in TMB-high NSCLC: a case report

Immune checkpoint inhibitors (ICIs) have transformed cancer therapy but are frequently associated with immune-related adverse events (irAEs), which complicate treatment decisions. Patients who experience severe irAEs are often excluded from further immunotherapy due to concerns of recurrence. However, rechallenging ICIs in selected patients under close monitoring may offer long-term benefits, although evidence remains limited and heterogeneous. We report a case of a 65-year-old man with stage IVB pulmonary adenocarcinoma harboring TP53 mutation and high tumor mutational burden. He initially received pembrolizumab-based chemoimmunotherapy but developed grade 4 hepatitis, requiring immunosuppressive treatment and discontinuation of ICIs. Subsequent tumor progression led to a rechallenge with ICIs alongside prophylactic tocilizumab. Although the patient experienced further grade 2 thyroiditis and grade 2 hypophysitis, all toxicities were manageable with hormone replacement and corticosteroids. A pacemaker was implanted for unrelated sick sinus syndrome. Despite intermittent symptoms, pembrolizumab monotherapy was maintained over a prolonged period, achieving durable tumor control with no progression noted at 4-year follow-up. This case highlights that ICI rechallenge can be a viable and effective treatment strategy in selected patients with prior high-grade irAEs, especially when initial toxicities are well controlled and alternative causes of symptoms are carefully excluded. The prophylactic use of agents like tocilizumab may reduce the risk of irAE recurrence. This underscores the need for individualized risk-benefit assessment and close clinical monitoring in rechallenge scenarios.