775 Immune Checkpoint Inhibitor Therapy in Patients With Preexisting Inflammatory Bowel Disease

Abstract

PURPOSE The risk of immune checkpoint inhibitor therapy-related GI adverse events in patients with cancer and inflammatory bowel disease (IBD) has not been well described. We characterized GI adverse events in patients with underlying IBD who received immune checkpoint inhibitors. PATIENTS AND METHODSWe performed a multicenter, retrospective study of patients with documented IBD who received immune checkpoint inhibitor therapy between January 2010 and February 2019. Backward selection and multivariate logistic regression were conducted to assess risk of GI adverse events. RESULTSOf the 102 included patients, 17 received therapy targeting cytotoxic T-lymphocyte antigen-4, and 85 received monotherapy targeting programmed cell death 1 or its ligand. Half of the patients had Crohn's disease, and half had ulcerative colitis. The median time from last active IBD episode to immunotherapy initiation was 5 years (interquartile range, 3-12 years). Forty-three patients were not receiving treatment of IBD. GI adverse events occurred in 42 patients (41%) after a median of 62 days (interquartile range, 33-123 days), a rate higher than that among similar patients without underlying IBD who were treated at centers participating in the study (11%; P , .001). GI events among patients with IBD included grade 3 or 4 diarrhea in 21 patients (21%). Four patients experienced colonic perforation, 2 of whom required surgery. No GI adverse event-related deaths were recorded. Anti-cytotoxic T-lymphocyte antigen-4 therapy was associated with increased risk of GI adverse events on univariable but not multivariable analysis (odds ratio, 3.19; 95% CI, 1.8 to 9.48; P = .037; and odds ratio, 4.72; 95% CI, 0.95 to 23.53; P = .058, respectively).CONCLUSION Preexisting IBD increases the risk of severe GI adverse events in patients treated with immune checkpoint inhibitors.

Immunobiology of Thymic Epithelial Tumors: Implications for Immunotherapy with Immune Checkpoint Inhibitors

“…In fact, patients with an AD or receiving an immunosuppressive therapy were usually excluded from clinical trials of ICIs, due to the possible risk for an autoimmune flare on ICIs and the reduced efficacy of ICI during immunosuppression. Nonetheless, subsequent experiences suggested that ICIs might be safe in selected patients with a preexisting AD and the onset of autoimmunity flares were manageable (exacerbation rate of 20-40%) [60][61][62]. As for the efficacy, small case series reported complete response in patients treated simultaneously with ICIs and selective immunosuppressant therapy (e.g., tocilizumab, vedolizumab, infliximab) [63,64], while nonselective immunosuppressant drugs (e.g., corticosteroids, tacrolimus, cyclophosphamide, mycophenolate mofetil) negatively affected the prognosis of patients on ICI [65].…”

“…Furthermore, patients with pre-existing ADs are at high-risk of autoimmune flares [60,62]. This theoretically applies also to patients with immune-mediated paraneoplastic syndromes, such as TET ones.…”

Incidence of immune checkpoint inhibitor–mediated diarrhea and colitis (imDC) in patients with cancer and preexisting inflammatory bowel disease: a propensity score–matched retrospective study

“…11 Another more recent study with 102 patients with IBD who received ICI therapy did not show an association between active GI disease within 3 months of immunotherapy and increased risk of GI adverse events (OR 1.53, 95% CI 0.52 to 4.46, p=0.437). 14 Second, we found that two of three patients with baseline inactive IBD and radiation history developed imDC but had a radiation exposure specifically to the sacroiliac area. Although history of radiation exposure itself did not show a signal for imDC in the entire cohort by multivariate Cox proportional-hazards model, it would be relevant to perform larger prospective studies to understand the interaction between abdominopelvic radiation and rates of imDC in the general population, as other studies have shown an implication for radiation therapy on both rates of irAEs and OS.…”

“…4 20 More recently, two studies on patients with IBD observed a 19% (4/21) incidence of immune-mediated colitis in one study 21 and a 21% (21/102) incidence of grade 3 or 4 diarrhea in another. 14 In addition, in previously published studies, discontinuation rates from all irAEs ranged from 0% to 29% in patients with autoimmune disorders, with anti-CTLA4 resulting in higher rates of irAEs than anti-PD1 monotherapy. 11 16 20 22 23 Among patients with IBD, discontinuation rates were 33% to 86%, and our study rates, 83.33%, fell on the higher end of that range.…”

“…[11][12][13] A recent multicenter, retrospective study of 102 patients with IBD receiving ICI therapy for various cancers detected a higher risk of developing GI-related adverse events as compared with patients without preexisting IBD (41% vs 11%, p<0.001). 14 Still, multiple outstanding questions remain in the rapidly evolving field of GI irAE surrounding treatment of patients with IBD, in particular, if the introduction of immunotherapy in an IBD cohort harms overall survival (OS). In this retrospective study, we aimed to measure the true incidence of IBD flare in patients with preexisting IBD and understand the influence of an irAE-related flare on toxicity-related or cancerrelated OS.…”