Patients With Digestive Disorders Are More Likely to Develop GI Toxicities on Immunotherapy

Patients with preexisting inflammatory bowel disease (IBD) have a significantly higher risk of developing gastrointestinal (GI) adverse events (AEs) during treatment with an immunotherapybased anticancer regimen than those without IBD, according to findings from a retrospective study.

Almost half (41%; 42 of 102) of patients with IBD who received an immune checkpoint inhibitor (ICI) developed a GI AE after a median of 62 days from treatment initiation, compared with 11% of the 11,377 patients without underlying IBD who were treated with CTLA-4 or PD-1/PD-L1 inhibitors (P < .001).

Among the 42 patients who experienced a GI AE, 23 discontinued immunotherapy and 15 developed additional GI-related toxicity after a median of 105 days from resolution of the initial AE. The most common reasons for discontinuation were disease progression (30%), completion of the treatment course (25%), and a GI-related AE (23%). Diarrhea affected 41 patients and half (51%) of them had a peak diarrhea grade of 3 or 4.

In univariate analysis, anti—CTLA-4 therapy correlated with an elevated risk for GI AEs versus anti–PD-1/PD-L1. Data showed that patients treated with a CTLA-4 inhibitor, whether as a monotherapy or in combination with other agents, were 3.19 times more likely to experience an AE (95% CI, 1.8-9.48; P = .037).

Investigators noted that in the multivariate analysis, anti—CTLA-4 therapy “showed a tendency” toward a significant association with AE risk (odds ratio [OR], 4.72; 95% CI, 0.95-23.53; P = .058). Similarly, IBD involving the colon also appeared to carry a higher likelihood for GI AEs than IBD (OR, 3.61; 95% CI, 0.85-15.27; P =.081).

Investigators defined IBD as Crohn disease (n = 49), ulcerative colitis (n = 49), or unclassified (n = 4). The 102 patients with IBD were treated with ICIs between January 2010 and February 2019. Patient data were collected from 14 participating institutions worldwide.

GI AEs observed in this study included diarrhea, colitis, nausea, and vomiting. Patients with IBD that was active 3 months before treatment initiation had higher grades of diarrhea than those with inactive IBD (P = .027).

Because patients with active IBD tended to have more severe GI AEs than patient with inactive IBD, investigators noted that treating underlying IBD prior to ICI-based therapy might be beneficial (Table). It is unclear whether clinicians should withhold immunotherapy until a patient’s IBD becomes inactive, they said.

Table. GI Toxicities in Active Versus Inactive IBD Within 3 Months of Immunotherapy (Click to Enlarge)

Although the rate of GI AEs for patients with preexisting IBD was high in the study, the advantages of ICI therapy “likely outweighed the risks.” Importantly, no GI toxicity-related deaths occurred in the cohort.

Most patients (85 of 102) with preexisting IBD were treated with PD-1/PD-L1 inhibitors. The remaining 17 patients received an anti—CTLA-4 agent.

The results from other retrospective studies have suggested a lower risk for GI AEs for patients with IBD on checkpoint therapy; however, those studies enrolled small populations and did not sufficiently characterize the underlying IBD, which made it difficult to generalize about GI AE risk, investigators said. They added that further studies with long-term follow-up that control for tumor type and other covariates are necessary to examine the links between IBD, immunotherapy, and subsequent GI toxicity.

Abu-Sbeih H, Faleck DM, Ricciuti B, et al. Immune checkpoint inhibitor therapy in patients with preexisting inflammatory bowel disease. J Clin Oncol. 2020;38(6):576-583. doi: 10.1200/JCO.19.01674.