P315 Gastrointestinal immune related adverse events associated with programmed-Death 1 blockade
Collins M.*1, Michot J.-M.2, Danlos F.-X.2, Champiat S.2, Mussini C.1, Soularue E.1, Mateus C.3, Loirat D.4, Buisson A.5, Rosa I.1,6, Lambotte O.1, Laghouati S.2, Voisin A.-L.2, Soria J.-C.2, Marabelle A.2, Robert C.2, Carbonnel F.1
1Paris Sud University, Le Kremlin Bicêtre, France 2Gustave Roussy Institute, Villejuif, France 3Gustave Roussy Institute, Department of Dermatology, Villejuif, France 4Paris V, Paris, France 5Clermont Ferrand University, Clermont ferrand, France 6Centre hospitalier Intercommunal de Créteil, Gastroenterology, Creteil, France
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
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).
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.
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.
 Champiat S., (2016), Management of immune checkpoint blockade dysimmune toxicities: a collaborative position paper. Ann Oncol
 Gupta A., (2015), review: colitis associated with anti-CTLA-4 therapy. Aliment Pharmacol Ther