Alice de Malet1, Guillemette Antoni2, Michael Collins3, Emilie Soularue3, Lysiane Marthey1, Thibaut Vaysse1, Clelia Coutzac4, Nathalie Chaput5, Christine Mateus6, Caroline Robert6, Franck Carbonnel7. 1. Department of Gastroenterology, Bicêtre Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), 94270, Le Kremlin-Bicêtre, France. 2. INSERM SC10-US19, Villejuif, France. 3. Department of Gastroenterology, Bicêtre Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), 94270, Le Kremlin-Bicêtre, France; University Paris-Saclay, Faculté de Médecine, Le Kremlin-Bicêtre, 94276, France. 4. Laboratory of Immunomonitoring in Oncology, CNRS-UMS 3655 and INSERM-US23, Gustave Roussy Cancer Campus, 114 Rue Edouard Vaillant, Villejuif, F-94805, France. 5. Laboratory of Immunomonitoring in Oncology, CNRS-UMS 3655 and INSERM-US23, Gustave Roussy Cancer Campus, 114 Rue Edouard Vaillant, Villejuif, F-94805, France; University Paris-Saclay, Faculté de Pharmacie, Chatenay-Malabry, F-92296, France. 6. Départment of Medecine, Dermatology Unit, Gustave Roussy Cancer Campus, 114 Rue Edouard Vaillant, Villejuif, F-94805, France. 7. Department of Gastroenterology, Bicêtre Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), 94270, Le Kremlin-Bicêtre, France; University Paris-Saclay, Faculté de Médecine, Le Kremlin-Bicêtre, 94276, France. Electronic address: franck.carbonnel@aphp.fr.
Abstract
BACKGROUND: Immune checkpoint inhibitors (ICIs), such as anti-CTLA-4 and anti-PD-1 antibodies, are effective against several malignancies. They are associated with gastrointestinal immune-related adverse events (GI-IrAEs), which may be severe and lead to ICI discontinuation. We assessed the risk of evolution of GI-IrAEs to chronic GI inflammation and the risk of recurrence after a second line of ICI. PATIENTS AND METHODS: This was a single-centre study. Included patients had a GI-IrAE due to ICIs between September 2010 and July 2017. We assessed the persistence of symptoms, endoscopic and/or histological inflammation, and the risk of recurrent GI-IrAEs after the second line of ICIs. RESULTS: Eighty patients were included. The median follow-up was 8.4 months (0.36-72.3). The median duration of GI symptoms was 1.5 months (5 days-10.3 months): 1.4 months (7 days-4.9 months) with anti-CTLA-4, 2.0 months (5 days-10.3 months) with anti-PD-1 and 1.0 month (8 days-3.4 months) with combination therapy (log-rank test: p = 0.02). Three and 6 months after the beginning of GI-IrAEs, 22% (95% confidence interval: 14%-33%) and 5.4% (2.0%-14.7%) of patients had persistent symptoms, respectively. After a median of 6 months, 20/27 patients had endoscopic and/or histological inflammation, of whom, seven were symptom free. After the first episode, 6/26 patients relapsed after receiving another course of ICIs. Among these 26, 89% (77%-100%) had no recurrence after 3 months, 71% or 95% if the second line was anti-CTLA-4 or anti-PD-1, respectively. CONCLUSION: GI-IrAEs seem to be acute or subacute, not chronic. Reintroduction of ICIs is possible in patients who had GI-IrAE.
BACKGROUND: Immune checkpoint inhibitors (ICIs), such as anti-CTLA-4 and anti-PD-1 antibodies, are effective against several malignancies. They are associated with gastrointestinal immune-related adverse events (GI-IrAEs), which may be severe and lead to ICI discontinuation. We assessed the risk of evolution of GI-IrAEs to chronic GI inflammation and the risk of recurrence after a second line of ICI. PATIENTS AND METHODS: This was a single-centre study. Included patients had a GI-IrAE due to ICIs between September 2010 and July 2017. We assessed the persistence of symptoms, endoscopic and/or histological inflammation, and the risk of recurrent GI-IrAEs after the second line of ICIs. RESULTS: Eighty patients were included. The median follow-up was 8.4 months (0.36-72.3). The median duration of GI symptoms was 1.5 months (5 days-10.3 months): 1.4 months (7 days-4.9 months) with anti-CTLA-4, 2.0 months (5 days-10.3 months) with anti-PD-1 and 1.0 month (8 days-3.4 months) with combination therapy (log-rank test: p = 0.02). Three and 6 months after the beginning of GI-IrAEs, 22% (95% confidence interval: 14%-33%) and 5.4% (2.0%-14.7%) of patients had persistent symptoms, respectively. After a median of 6 months, 20/27 patients had endoscopic and/or histological inflammation, of whom, seven were symptom free. After the first episode, 6/26 patients relapsed after receiving another course of ICIs. Among these 26, 89% (77%-100%) had no recurrence after 3 months, 71% or 95% if the second line was anti-CTLA-4 or anti-PD-1, respectively. CONCLUSION: GI-IrAEs seem to be acute or subacute, not chronic. Reintroduction of ICIs is possible in patients who had GI-IrAE.
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