M Collins1, J M Michot2, F X Danlos2, C Mussini3, E Soularue1, C Mateus4, D Loirat5, A Buisson6, I Rosa7, O Lambotte8, S Laghouati9, N Chaput10, C Coutzac10, A L Voisin9, J C Soria2, A Marabelle2, S Champiat2, C Robert4, F Carbonnel11. 1. Department of Gastroenterology, Kremlin Bicêtre Hospital, Assistance Publique-Hopitaux de Paris, Le Kremlin Bicêtre;; Paris Sud University, Le Kremlin Bicêtre. 2. Drug Development Department, Gustave Roussy, Villejuif. 3. Paris Sud University, Le Kremlin Bicêtre;; Department of Pathology, Kremlin Bicêtre Hospital, Assistance Publique-Hopitaux de Paris, Le Kremlin Bicêtre. 4. Dermatology Unit, Department of Medical Oncology, Gustave Roussy, Villejuif. 5. Department of Oncology, Curie Oncologic Institute, Paris. 6. Department of Gastroenterology, CHU Estaing, Clermont-Ferrand. 7. Department of Gastroenterology, Centre Hospitalier Intercommunal de Créteil, Créteil. 8. Paris Sud University, Le Kremlin Bicêtre;; Department of Internal Medicine, Kremlin Bicêtre Hospital, Assistance Publique-Hopitaux de Paris, Le Kremlin Bicêtre;; CEA, DSV/iMETI, Division of Immuno-Virology, IDMIT, Paris;; Inserm, U1184, Center for Immunology of Viral Infections and Autoimmune Diseases, Paris. 9. Pharmacovigilance Unit, Gustave Roussy, Paris Sud University, Villejuif. 10. Paris Sud University, Le Kremlin Bicêtre;; Laboratory of Immunomonitoring in Oncology, and CNRS-UMS 3655 and INSERM-US23, Gustave Roussy Cancer Campus, Villejuif, France. 11. Department of Gastroenterology, Kremlin Bicêtre Hospital, Assistance Publique-Hopitaux de Paris, Le Kremlin Bicêtre;; Paris Sud University, Le Kremlin Bicêtre;. Electronic address: franck.carbonnel@aphp.fr.
Abstract
BACKGROUND: Immune check-point blockade agents have shown clinical activity in cancer patients but are associated with immune-related adverse events that could limit their development. The aim of this study was to describe the gastrointestinal immune-related adverse events (GI-irAE) in patients with cancer treated with anti-PD-1. METHODS: this is a retrospective study of consecutive adult patients who had a suspected GI-irAE due to anti-PD-1 antibodies between 2013 and 2016. Patients were recruited through a pharmacovigilance registry. Patients' data were reviewed by a multidisciplinary committee that included gastroenterologists, oncologists and a pathologist. Quantitative variables are described by median (range), qualitative variable by frequency (percentage). RESULTS: Forty-four patients were addressed to a Gastroenterology unit for a suspected GI-IrAE. Twenty patients had a confirmed GI-irAE related to anti-PD-1, which occurred 4.2 months (0.2; 22.1) after the initiation of anti-PD-1. GI-IrAE incidence rate under anti-PD-1 treatment was estimated to be 1.5%. Among patients with GI-IrAE, main symptoms were diarrhoea (n = 16, 80%), abdominal pain (n = 13, 65%), nausea and vomiting (n = 11, 55%), intestinal obstruction (n = 1, 5%), and haematochezia (n = 2, 10%). No patient had colectomy. Four distinct categories of GI-irAE were observed: acute colitis (n = 8, 40%), microscopic colitis (n = 7, 35%), upper gastrointestinal tract inflammation (n = 4, 20%) and pseudo-obstruction (n = 1, 5%). Response rates to corticosteroids were 87.5% (7/8) in acute colitis, 57% (4/7) in microscopic colitis and 75% (3/4) in upper gastrointestinal tract inflammation. Median time to resolution was 36 days (6-172) in acute colitis, and 98 days (42-226) in microscopic colitis. CONCLUSION: This study suggests that GI-irAE are different and less frequent with anti PD-1 than with anti CTLA-4.
BACKGROUND: Immune check-point blockade agents have shown clinical activity in cancer patients but are associated with immune-related adverse events that could limit their development. The aim of this study was to describe the gastrointestinal immune-related adverse events (GI-irAE) in patients with cancer treated with anti-PD-1. METHODS: this is a retrospective study of consecutive adult patients who had a suspected GI-irAE due to anti-PD-1 antibodies between 2013 and 2016. Patients were recruited through a pharmacovigilance registry. Patients' data were reviewed by a multidisciplinary committee that included gastroenterologists, oncologists and a pathologist. Quantitative variables are described by median (range), qualitative variable by frequency (percentage). RESULTS: Forty-four patients were addressed to a Gastroenterology unit for a suspected GI-IrAE. Twenty patients had a confirmed GI-irAE related to anti-PD-1, which occurred 4.2 months (0.2; 22.1) after the initiation of anti-PD-1. GI-IrAE incidence rate under anti-PD-1 treatment was estimated to be 1.5%. Among patients with GI-IrAE, main symptoms were diarrhoea (n = 16, 80%), abdominal pain (n = 13, 65%), nausea and vomiting (n = 11, 55%), intestinal obstruction (n = 1, 5%), and haematochezia (n = 2, 10%). No patient had colectomy. Four distinct categories of GI-irAE were observed: acute colitis (n = 8, 40%), microscopic colitis (n = 7, 35%), upper gastrointestinal tract inflammation (n = 4, 20%) and pseudo-obstruction (n = 1, 5%). Response rates to corticosteroids were 87.5% (7/8) in acute colitis, 57% (4/7) in microscopic colitis and 75% (3/4) in upper gastrointestinal tract inflammation. Median time to resolution was 36 days (6-172) in acute colitis, and 98 days (42-226) in microscopic colitis. CONCLUSION: This study suggests that GI-irAE are different and less frequent with anti PD-1 than with anti CTLA-4.
Authors: T Sakakida; T Ishikawa; Y Chihara; S Harita; J Uchino; Y Tabuchi; S Komori; J Asai; T Narukawa; A Arai; H Tsunezuka; T Kosuga; H Konishi; M Moriguchi; H Yasuda; F Hongo; M Inoue; S Hirano; O Ukimura; Y Itoh; T Taguchi; K Takayama Journal: Clin Transl Oncol Date: 2019-10-01 Impact factor: 3.405
Authors: Alberto Pavan; Lorenzo Calvetti; Alessandro Dal Maso; Ilaria Attili; Paola Del Bianco; Giulia Pasello; Valentina Guarneri; Giuseppe Aprile; PierFranco Conte; Laura Bonanno Journal: Oncologist Date: 2019-04-23