Evolution and recurrence of gastrointestinal immune-related adverse events induced by immune checkpoint inhibitors

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.

Keywords: Drug toxicity; Gastrointestinal toxicity; Immunotherapy.