Immune Checkpoint Inhibitor Colitis Research Articles

Mucosal inflammation predicts response to systemic steroids in immune checkpoint inhibitor colitis

BackgroundImmune-related colitis is a common, often serious complication of immune checkpoint inhibition (ICI). Although endoscopy is not strictly recommended for any grade of diarrhea/colitis, emerging evidence suggests that endoscopic evaluation...

Use of Fecal Microbial Transplantation for Immune Checkpoint Inhibitor Colitis

ABSTRACTImmune checkpoint inhibitors (ICIs) can result in immune-related adverse events which require rapid identification and treatment. Gastrointestinal immune-related adverse events are among the most frequent and severe of these events. ICI colitis can be refractory to current therapies such as corticosteroids and biologic therapy. Fecal microbiota transplantation (FMT) is currently used in cases of recurrent Clostridioides difficile colitis. Many investigations are underway to test the utility of FMT for additional indications, including inflammatory bowel disease (IBD). We present a 71-year-old man with ICI colitis that was nonresponsive to currently defined management options and treated with benefit from FMT.

Association of vitamin D intake with decreased risk of immune checkpoint inhibitor-induced colitis.

89 Background: There is a lack of predictive markers informing on the risk of colitis in patients treated with immune checkpoint inhibitors (ICIs). The aim of this study was to identify potential factors associated with development of ICI colitis. Methods: We performed a retrospective analysis of melanoma patients at Dana-Farber Cancer Institute who received PD-1, CTLA-4, or combination blockade between May 2011 to October 2017. Clinical and laboratory characteristics associated with pathologically confirmed ICI colitis were evaluated using multivariate logistic regression analyses. External validation was performed on an independent cohort from Massachusetts General Hospital. Results: The discovery cohort included 213 patients of whom 37 developed ICI colitis (17%). The odds of colitis were higher in patients treated with ipilimumab either as monotherapy or in combination with nivolumab compared to those treated with pembrolizumab. Vitamin D use was recorded in 66/213 patients (31%) before starting ICIs. In multivariable regression analysis, vitamin D use conferred significantly reduced odds of developing ICI colitis (OR 0.35, 95% CI 0.1–0.9). These results were confirmed in the validation cohort of 169 patients of whom 49 developed ICI colitis (29%). Pretreatment neutrophil/lymphocyte ratio (NLR) ≥5 predicted reduced odds of colitis (OR 0.34, 95% CI 0.1–0.9) only in the discovery cohort. Conclusions: This is the first study to report that among patients treated with ICIs, vitamin D intake is associated with reduced risk for ICI colitis. This finding is consistent with prior reports of prophylactic use of vitamin D in ulcerative colitis and GVHD. This observation should be validated prospectively in future studies. [Table: see text]

High prevalence of IBD-associated genetic variants in patients (pts) with immune checkpoint inhibitor (ICI) enteritis/colitis.

2582 Background: Colitis is a frequent toxicity of ICI therapy but there is paucity of data on risk factors. Specific serological markers and genetic polymorphisms have been associated with inflammatory bowel disease (IBD) (ulcerative colitis, Crohn’s disease). However, the prevalence of these markers in pts with ICI colitis is unknown. We performed a pilot study to determine the prevalence of IBD-associated genetic and serologic biomarkers in pts with ICI colitis. Methods: Cancer pts with histologically confirmed ICI enteritis/colitis and no history of IBD underwent commercial IBD panel testing. The panel included 4 genetic markers ( ATG16L1, NXK2–3, ECM1, STAT3), 8 serological markers (anti-A4-Fla2, anti-A4-FlaX, anti-CBir1, anti-OmpC, ASCAIgA, ASCA-IgG, pANCA, ANCA), and 5 inflammatory markers (vascular endothelial growth factor [VEGF], intracellular adhesion molecule 1[ICAM-1], vascular cell adhesion molecule 1 [VCAM-1], C-reactive protein, serum amyloid A [SAA]). Clinical testing on serum samples was performed by Prometheus Laboratories (San Diego, CA). Results: Of 15 cancer pts with biopsy confirmed ICI colitis, 10 (67%) were homozygous for 1 or more of 4 genetic markers. The remaining 5 pts were all heterozygous for two or more of the genetic markers. One or more serologic markers associated with IBD were elevated in 7/15 (47%) pts. Serum reactivity was noted for ASCA-IgA (1/15, 7%), ASCA-IgG (1/15, 7%), anti-OmpC (3/15, 20%), anti-CBR IgG (2/15, 13%), anti-A4-FlaX (1/15, 7%), and ANCA (2/15, 13%). One or more inflammatory markers were elevated in 13/15 (88%) pts. Elevations in VEGF, VCAM-1, ICAM-1, and SAA were noted in 2 (13%), 8 (53%), 8 (53%), and 11 (73%) pts, respectively. Only 6 (40%) pts had elevations in CRP levels despite the presence of active inflammation on biopsy. The IBD panel was reported as being consistent with Crohn’s disease in 2 pts, ulcerative colitis in 1 pt and inconclusive for type but consistent with IBD in 1 pt. Conclusions: In this pilot study, all patients with ICI colitis, were either homozygous or heterozygous for two or more high risk IBD alleles. If validated, such testing may prospectively identify pts at risk for developing ICI colitis.

Immune checkpoint inhibitor colitis: the flip side of the wonder drugs.

Immune checkpoint inhibitors block the co-inhibitory receptors on T cells to activate their cytotoxic immune function and are rapidly being explored for the treatment of various advanced-stage malignancies. These novel drugs have already significantly increased survival rates. The first available immune checkpoint inhibitors were cytotoxic T lymphocyte antigen 4 (CTLA-4) inhibitors (such as ipilimumab), followed by programmed cell death protein 1 (PD-1) and programmed cell death protein ligand 1 (PD-L1) inhibitors (such as pembrolizumab and nivolumab). Anti-PD-1 and anti-PD-L1 therapies have demonstrated better efficacy and tolerability and less severe adverse effects compared to anti-CTLA-4 agents. Idelalisib, a PI3Kδ isoform inhibitor, is another immunotherapeutic agent that is often classified separately and is currently used in treatment of chronic lymphocytic leukemia and non-Hodgkin lymphomas. Despite successful therapeutic responses, immune-related adverse events have been reported with the use of these agents. The gastrointestinal side effects, particularly diarrhea, are among the most commonly reported symptoms. The histologic features of immune checkpoint inhibitor-associated colitis show a spectrum of patterns of injury among various drug classes. There is significant overlap between immune checkpoint inhibitor-associated colitis and other colitides, making the differential diagnosis difficult-especially in the absence of clinical history. The histopathology data on immune checkpoint inhibitor-associated colitis are limited. Here we review clinical features as well as various histologic patterns of colitis associated with these groups of medications.