Evaluation of gastrointestinal and hepatic immune-related adverse events associated with nivolumab plus ipilimumab for unresectable advanced/recurrent pleural mesothelioma in Japan

Nivolumab plus ipilimumab is a first-line treatment option for unresectable advanced or recurrent pleural mesothelioma (PM); however, real-world safety data remain limited. Gastrointestinal and hepatic immune-related adverse events (irAEs) were prespecified as key safety endpoints in the Japanese post-marketing surveillance (PMS) program because of their clinical significance. This study aimed to characterize the incidence, time to onset, management, and outcomes of diarrhea/colitis/gastrointestinal perforation and liver disorder in Japanese patients with PM receiving nivolumab plus ipilimumab in routine clinical practice. The PMS included 75 patients with unresectable advanced or recurrent PM who received nivolumab plus ipilimumab between October 2021 and December 2022. Treatment-related adverse events were collected over 6 months, and gastrointestinal and hepatic events were identified using predefined criteria. The incidences of diarrhea/colitis/gastrointestinal perforation and liver disorder were 12.0% and 10.7%, respectively, with Grade ≥ 3 events in 1.3% and 6.7%. Most patients with diarrhea/colitis/gastrointestinal perforation received treatment, and their events had resolved or were resolving. Among patients with liver disorder, 62.5% received treatment, and most events had resolved or were resolving. No new gastrointestinal or hepatic safety concerns were identified. These findings provide evidence on the timing and management of these irAEs and may support toxicity monitoring and treatment decision-making.