Background: Immunotherapy for cancer is coming of age. The main class of check-point blockade agents, anti-Programmed-death 1 (PD-1) antibodies, is associated with various immune-related adverse events. The aim of this study was to describe the gastrointestinal immune-related adverse events (GI-irAE) associated with anti PD-1
Methods: This is a retrospective study of all consecutive adult patients who had a suspected GI-irAE related to anti-PD-1 antibody between 2013 and 2016. Patients were recruited through a pharmacovigilance registry (REISAMIC). Data was reviewed by a multidisciplinary team, including a pathologist who reviewed endoscopic biopsies. Frequency calculation was restricted to Gutave Roussy patients. Quantitative variables are described by median (range), qualitative variable by frequency (percentage).
Results: From January 2013 to August 2016, 909 patients received anti-PD1 or anti-PDL1 at Gustave Roussy. 43 consecutive patients with digestive symptoms were screened to search for GI-irAE. Finally, nineteen patients had a confirmed GI-irAE related to anti-PD-1 treatment. Frequency of GI-IrAE was therefore 19/909 (1.3%). Median time between first infusion of anti PD-1 and onset of GI-IrAE was 4.3 [1–33] months. Symptoms were diarrhea (n=16, 84%), abdominal pain (n=13, 68%), nausea and vomiting (n=8, 42%), severe constipation (n=2), and hematochezia (n=2). Lower endoscopy was normal in 7 patients (36%); it showed erythema in 5 patients (26%) and ulcerations in three patients (16%). All endoscopic lesions were accessible to a flexible sigmoidoscopy. GI-irAE associated with anti PD-1 could be classified into 4 distinct clinicopathological entities: acute colitis (n=8), microscopic colitis (n=7), severe ulcerative gastritis (n=2) and coprostasis (n=2). One patient with coprostasis died from necrotizing enterocolitis. Response rates to corticosteroids were of 87.5% (7/8) in acute colitis (resolution of symptoms in 36 days (6–172)) and of 57% (4/7) in microscopic colitis (resolution of symptoms in 98 days (42–226)), respectively.
Conclusions: This study suggests that GI-IrAE associated with anti PD-1 are much less frequent than with anti CTLA-4 (1.3% vs 8–20%) . It describes four entities with distinct features and outcomes, the most frequent being acute colitis and microscopic colitis.
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