Safety of Immune Checkpoint Inhibitors for Cancer Therapy in IBD Patients

Abstract

Listen

Translate article

Introduction: Cancers exploit inhibitory pathways of the immune system to shield themselves from a host attack. Immune checkpoint inhibitors (ICIs) are novel drugs that block these inhibitory pathways allowing a host immune response against the tumor. ICIs are indicated against more than ten types of cancer; the number of approved ICIs and indications for their use are rapidly expanding due to their efficacy as cancer therapies. However, ICIs carry a risk of inflammation of non-tumor tissue. These “immune-related adverse events” (irAEs) can be lethal and affect any host tissue. Patients with pre-existing immune conditions were excluded from all ICI trials. Given the increasingly common use of ICIs, it is necessary to define the safety of these drugs in this population. We report the outcomes of patients with pre-existing inflammatory bowel disease (IBD) treated with ICIs. Methods: This is a retrospective review of all adult patients at the University of Chicago Medicine who received one of the six FDA-approved ICIs (nivolumab, pembrolizumab, ipilimumab, atezolizumab, avelumab, durvalumab) and carried a previously confirmed diagnosis of IBD. Results: 6 patients with IBD (2CD, 4 UC, median age 63y, range 54-89) received ICIs. 3 patients (2 UC, 1 CD) developed severe colitis after ICI initiation requiring discontinuation of the ICI, with two requiring hospitalization. One of these patients had not been on IBD therapy at baseline, one was treated with mesalamine and the other with 6MP. After developing irAEs, 2/3 patients were treated with corticosteroids and one required vedolizumab. Of the 3 patients (2 UC, 1 CD) who did not develop irAEs, one had an ileostomy, one had therapy proactively changed to vedozliumab (from IFX/AZA) and one remained on sulfasalazine. Conclusion: In this small series, 3/6 IBD patients required ICI discontinuation due to irAEs. All cases of irAEs consisted of colitis. Severe colitis requiring hospitalization occurred in 2/6 patients. One patient was proactively treated with vedolizumab, an anti-a4β7-integrin that blocks leukocyte extravasation in the gut, during ICI therapy with the intent of protecting the gut from inflammation while allowing for an extra-intestinal anti-tumor response. Vedolizumab should be investigated as a tool to reduce the risk of colitis in IBD patients undergoing ICI therapy for extra-intestinal tumors.728 Figure 1 No Caption available.