Immune Checkpoint Inhibitor Colitis Research Articles

Follow-up biopsies in gastrointestinal immune checkpoint inhibitor toxicity may show markedly different inflammatory patterns than initial injury

Colitis is a common manifestation of immune checkpoint inhibitor (ICI) toxicity and can present with varied histologic patterns of inflammation, some of which have been shown to be associated with specific ICI drug types. Although the histologic features of ICI colitis seen at the time of diagnosis have been described, there have been few reports following these patients over time. We evaluated initial and follow-up biopsies in 30 patients with ICI colitis and found that 37% of patients developed a different pattern of injury on follow-up biopsy compared to the initial biopsy. Patients with a different inflammatory pattern were more likely to have restarted ICI therapy before their follow-up biopsy (64%) compared to those without a change in inflammatory pattern (11%; P < 0.01). The majority of these patients had changed ICI drug types (86%). Additionally, many cases changed to an inflammatory bowel disease (IBD)-like pattern (36%), raising a question of de novo IBD. However, all of our patients with an IBD-like pattern experienced sustained resolution of symptoms without steroids or other immunosuppressive medications following discontinuation of ICI therapy, consistent with a diagnosis of ICI toxicity. Our findings suggest that follow-up biopsies in patients with ICI colitis may show a different histology and that this does not necessarily warrant a change in the histologic diagnosis to another disease.

Immune Checkpoint Inhibitor Colitis, a Rising Issue in Targeted Cancer Therapy Era: A Literature Review.

Research advances in the oncology treatment field have led to the widespread use of immunotherapy. The usage of immune checkpoint inhibitor (ICI) has improved the survival of cancer patients with metastases. This has also led to the rapidly expanding indications for ICI use. However, ICI usage may lead to toxicity, which may be immune-related, in different organ-specific targets. The immune-related adverse events (irAEs) of ICI may lead to increased morbidity, decreased quality of life, and early termination of ICI. The clinical manifestations of irAEs in the gastrointestinal system are variable, ranging from self-limited to life-threatening or fatal events. In this review article, we would like to focus on discussing ICI-induced colitis, which is one of the most common ICI irAEs in the gastrointestinal tract.

P641 Faecal calprotectin determines non-response to corticosteroids in patients with immune checkpoint inhibitor colitis

Abstract Background Immune checkpoint inhibitor (ICI) therapy has improved survival outcomes in patients with advanced malignancy. ICI colitis (ICI-C) is one of the most common adverse events which often leads to cessation of an otherwise effective therapy.1,2 Corticosteroid therapy remains first-line treatment in patients with ICI-C. The aim of this study was to assess predictors of non-response to corticosteroid therapy to help guide early escalation to biologic therapy. Methods Multicentre retrospective analysis of adults hospitalized with ICI-C between July 2018 to March 2023. ICI-C was defined by patients who had current or prior immunotherapy who presented with diarrhoea with negative infective faeces PCR testing and admission diagnosis of ICI-C by their treating Physician. Baseline demographic, clinical, biochemical, and endoscopic data were collected. Grading of clinical severity on presentation and response to immunosuppression was defined by CTCAE diarrhoea grading with response defined as improvement to grade 1 or less. Results 82 patients were analysed. 31 (38%) female, median age was 65.5 years (IQR 59-72)], 27 (33%) failed corticosteroid therapy and required biologic therapy. 34 (42%) had a faecal calprotectin on admission. On univariable analysis faecal calprotectin emerged as the sole predictor of corticosteroid non-response. ROC analysis identified an optimal faecal calprotectin cut-off of 620 mcg/g to identify corticosteroid non-responders [Sensitivity 75% (57.6-92.7), Specificity 77.8% (52.4-93.6), Accuracy 76.5%, PLR 3.37 (1.36-8.38), NLR 0.32 (0.13-0.78), AUROC 0.76 (0.616-0.911), OR 10.5 (2.24-49.3), PPV 75 (47.6-92.7), NPV 77.8 ( 52.4-93.6)].12/16 (75%) of patients with a faecal calprotectin ≥ 620 required biologic therapy. Conclusion Faecal calprotectin is a predictor of non-response to corticosteroid therapy in patients with immune checkpoint inhibitor colitis. This study identified a faecal calprotectin threshold of 620mcg/g as the optimal cut-off to identify corticosteroid non-response and need for second-line immunosuppression. These findings may help to reduce the need for endoscopic assessment and guide early escalation to biologic therapy. REFERENCES: 1. Fujii T, Colen RR, Bilen MA, et al. Incidence of immune-related adverse events and its association with treatment outcomes: The MD Anderson Cancer Center experience. Invest New Drugs. 2018;36(4):638-646. doi:10.1007/s10637-017-0534-0 2. Wang Y, Abu-Sbeih H, Mao E, et al. Endoscopic and Histologic Features of Immune Checkpoint Inhibitor-Related Colitis. Inflamm Bowel Dis. 2018;24(8):1695-1705. doi:10.1093/ibd/izy104.

Role of proton pump inhibitors in immune checkpoint inhibitor colitis.

743 Background: Proton pump inhibitors (PPIs) are known to be beneficial in symptomatic control of gastroesophageal reflux disease and gastritis which can be a common complication of various cancers specifically gastrointestinal (GI) cancers. Microscopic colitis development has been studied to be associated with PPI use. Immune checkpoint Inhibitor (ICI) colitis is a known adverse effect of Inhibitors of Programmed cell death 1 (PD-1) and its ligand (PD-L1). Previous studies have also shown use of PPIs and NSAIDs are common risk factors which can exacerbate ICI Colitis caused by Inhibitors of PD-1 and PD-L1. This study is designed to observe association of certain drugs especially PPIs in ICI colitis. Methods: This is a single center, retrospective, and observational study that investigated patients treated with PD-1 and PD-L1 Inhibitors for management of any type of cancer between January 2022- September 2023. A list of patients treated with PD-1 and PD-L1 inhibitors was obtained from Inpatient pharmacy records followed by retrospective chart review to look for symptoms of colitis and other medications used by each patient. Primary outcome was to observe the role of PPIs in ICI colitis. Secondary outcomes were to observe the number of patients with GI cancers on PPIs who developed colitis. We also observed the effect of NSAIDs use as a potential risk factor in the population with ICI colitis. Results: The data consisted of 93 patients of which 17 (18.3%) developed colitis. Among this population 13 (76.5%) was ICI colitis, 2 (11.7%) was diverticular colitis and 2 (11.7%) was Infectious colitis. PPI use was seen in 3 out of 13 patients (23%) with ICI colitis. Patients with any type of GI cancer who developed colitis was 5 (25%) and PPI use in ICI colitis was seen in 2 out of these 5 patients. NSAIDs use was seen in 3 (23%) patients with ICI colitis. Conclusions: We did not observe significant association between PPI use and ICI colitis. ICI use becoming increasingly common in oncologic population, larger studies may be needed to further evaluate risk factors associated with ICI colitis in this population.

S228 Fecal Transplantation Improved Patients' Reported Outcome After Immune Checkpoint Inhibitor Colitis

S228 Fecal Transplantation Improved Patients' Reported Outcome After Immune Checkpoint Inhibitor Colitis

S314 Efficacy of Infliximab and Vedolizumab in Immune Checkpoint Inhibitor Colitis: A Meta-Analysis

S314 Efficacy of Infliximab and Vedolizumab in Immune Checkpoint Inhibitor Colitis: A Meta-Analysis

S226 Genetic Risk for Colorectal Cancer Is Associated With Earlier Onset and Higher Incidence of Immune Checkpoint Inhibitor Colitis

S226 Genetic Risk for Colorectal Cancer Is Associated With Earlier Onset and Higher Incidence of Immune Checkpoint Inhibitor Colitis

Highly multiplexed spatial analysis identifies tissue-resident memory T cells as drivers of ulcerative and immune checkpoint inhibitor colitis

Colitis is a prevalent adverse event associated with immune checkpoint inhibitor (ICI) therapy with similarities to inflammatory bowel disease. Incomplete mechanistic understanding of ICI colitis curtails evidence-based treatment. Given the often-overlooked connection between tissue architecture and mucosal immune cell function, we here applied imaging mass cytometry (IMC) to gain spatial proteomic insight in ICI colitis in comparison to ulcerative colitis (UC). Using a cell segmentation pipeline that simultaneously utilizes high-resolution nuclear imaging and high-multiplexity IMC, we show that intra-epithelial CD8+ Tcells are significantly more abundant (and numerically dominant) in anti-PD-1± anti-CTLA-4-induced colitis compared to anti-CTLA-4-induced colitis and UC. We identified activated, cycling CD8+ tissue-resident memory T(RM) cells at the lamina propria-epithelial interface as drivers of cytotoxicity in ICI colitis and UC. Moreover, we found that combined ICI-induced colitis featured highest granzyme B levels both in tissue and serum. Together, these data reinforce CD8+ TRM cells as potentially targetable drivers of ICI colitis.

Gastrointestinal mucosal toxicities from immune checkpoint inhibitors: Current understanding and future directions.

Immune checkpoint inhibitor (ICI) therapy has revolutionized the field of oncology over the past decade, leading to durable remissions in some patients but also producing a wide spectrum of treatment-limiting inflammatory toxicities that are referred to as immune-related adverse events (irAEs). Although irAEs can involve any organ system in the body, they most commonly affect the barrier tissues, including the gastrointestinal tract with colitis and enterocolitis affecting a significant fraction of patients on ICIs. We are beginning to understand the mechanisms that drive ICI colitis, with early experiments indicating a role for CD8+ resident memory T cells (TRMs) in the gut, which become activated and differentiate into cytotoxic cells in response to ICI therapy. The risk factors that define who will develop ICI colitis are not understood and substantial efforts are underway to identify potential biomarkers for risk of this and other toxicities. Optimal management of ICI colitis is also an area of active investigation. Current standard treatments are based largely on small, retrospective analyses, and while drugs like systemic glucocorticoids or the TNFα inhibitor infliximab do appear to be highly active in ICI colitis, the impact of these therapies on antitumor responses is poorly understood. As discussed in this review, future work will have to define the immune mechanisms driving ICI colitis in more detail and in comparison to antitumor responses in order to identify candidate pathways that can be targeted to improve ICI colitis without interfering in antitumor immunity. Studying these interventions will require randomized, controlled trials with both tumor and colitis endpoints, a goal that will necessitate collaboration across institutions and funding agencies. We are at a point where such collaborative trials are feasible, and have the potential to greatly improve the care of patients with ICI colitis as well as other irAEs.

Effect of fecal transplantation on patients’ reported outcome after immune checkpoint inhibitor colitis.

2645 Background: The use of fecal microbiota transplantation (FMT) has traditionally been reserved for the treatment of recurrent Clostridioides difficile infections (CDI). As the gut microbiome has been increasingly acknowledged to play a role in a variety of bodily processes, FMT has seen its application extended to other gastrointestinal disorders. Immune-mediated colitis (IMC) is a similar entity to inflammatory bowel disease and arises as a side effect of immune checkpoint inhibitor therapy to stimulate the immune response. Treatment of IMC is mostly limited to immunosuppressants e.g. corticosteroids, infliximab, and vedolizumab. Cases refractory to such medications pose a significant challenge. FMT has been shown to be a successful treatment in refractory IMC in small case series, further large studies are needed to determine its efficacy. Methods: We measured the efficacy of FMT for refractory IMC among 47 patients via chart review and clinical assessment and patients’ reported outcome (PRO) via established MD Anderson Symptom Inventory (MDASI). Among them, 9 patients had concurrent CDI as well at the time of diagnosis. Results: Forty-seven patients were included in our study. Most patients had a peak diarrhea grade ≥ 3 (93.6%) and colitis grade ≥ 2 (91.5%). Ulcerous (23, 49.0%) and non-ulcerous (12, 25.5%) inflammation were the predominant endoscopic findings. 45 (95.7%) patients received corticosteroids, and 43 patients (91.5%) received add-on infliximab or vedolizumab. IMC symptom response was 85.1% after FMT with median time to response of 4.5 days. The transient complications rate is 34.0% at 7 days and 17.0% at 30 days. Response rate among the 38 patients without concurrent CDI was 86.8%. Forty-one (87.2%) patients demonstrated clinical remission by the end of the study period. On the PRO analysis, we observed a favorable trend of significant patient-reported symptom reduction on diarrhea during 12 weeks after FMT, along with improved daily physical functioning on working. Conclusions: FMT may serve as a potential treatment option in IMC refractory to standard treatment to avoid long-term steroid dependency and immunosuppression. It is effective to maintain IMC remission with a low complication rate. The role of the gut microbiome in cancer and the implications for FMT remain uncertain and need further elucidation. Clinical trial information: NCT03819296 . [Table: see text]

Immune-Related Adverse Events of the Gastrointestinal System.

Immune checkpoint inhibitors (ICI) are a form of immunotherapy that have revolutionized the treatment of a number of cancers. Specifically, they are antibodies targeted against established and emerging immune checkpoints, such as cytotoxic T-cell antigen 4 (CTLA4), programmed cell death ligand 1 (PD-L1) and programmed cell death 1 protein (PD-1) on CD8-positive T cells, which promote the destruction of tumor cells. While the immune checkpoint inhibitors are very effective in the treatment of a number of cancers, their use is limited by serious and in some cases life-threatening immune-related adverse events. While these involve many organs, one of the most prevalent serious adverse events is immune checkpoint inhibitor colitis, occurring in a significant proportion of patients treated with this therapy. In this review, we aim to broadly describe the immune-related adverse events known to occur within the gastrointestinal system and the potential role played by the intestinal microbiome.

Accelerated curation of checkpoint inhibitor-induced colitis cases from electronic health records.

Automatically identifying patients at risk of immune checkpoint inhibitor (ICI)-induced colitis allows physicians to improve patientcare. However, predictive models require training data curated from electronic health records (EHR). Our objective is to automatically identify notes documenting ICI-colitis cases to accelerate data curation. We present a data pipeline to automatically identify ICI-colitis from EHR notes, accelerating chart review. The pipeline relies on BERT, a state-of-the-art natural language processing (NLP) model. The first stage of the pipeline segments long notes using keywords identified through a logistic classifier and applies BERT to identify ICI-colitis notes. The next stage uses a second BERT model tuned to identify false positive notes and remove notes that were likely positive for mentioning colitis as a side-effect. The final stage further accelerates curation by highlighting the colitis-relevant portions of notes. Specifically, we use BERT's attention scores to find high-density regions describing colitis. The overall pipeline identified colitis notes with 84% precision and reduced the curator note review load by 75%. The segment BERT classifier had a high recall of 0.98, which is crucial to identify the low incidence (<10%) of colitis. Curation from EHR notes is a burdensome task, especially when the curation topic is complicated. Methods described in this work are not only useful for ICI colitis but can also be adapted for other domains. Our extraction pipeline reduces manual note review load and makes EHR data more accessible for research.

Colon Adenoma After Diagnosis of Immune Checkpoint Inhibitor-mediated Colitis.

Purpose: While the occurrence of colitis during immune checkpoint inhibitor (ICI) treatment is recognized as a sign of robust immune activation and correlates with better oncological outcomes, the long-term impact of ICI-mediated colitis on the colonic mucosa has not been studied. We thus aim to describe the colonoscopy and histology findings in patients at a follow-up time of ≥ 6 months post initial colitis event. Methods: This retrospective analysis included adult cancer patients diagnosed with ICI colitis at a tertiary cancer center between October 2013 and June 2020. The study group included patients diagnosed with immune mediated colitis who had also undergone a follow up colonoscopy or flex sigmoidoscopy. The control group was patients exposed to ICI without immune mediated colitis. We reported patients' colitis clinical course, treatment, outcomes, and endoscopic and histologic features at diagnosis and at follow-up time of ≥ 6 months. Results: Total 39 patients met the study criteria, with 82% being male, and 35.8% having melanoma. Most patients received a combination of CTLA-4 and PD-1/L1 inhibitors (82%). On initial endoscopic evaluation, inflammation without ulceration was reported in 76.9% of patients and active inflammation on histologic examination in 79.3% of patients. Most patients (79.4%) received corticosteroids, and 56.4% received add-on selective immunosuppressive therapy. Four patients received fecal microbiota transplantation. On follow-up, new incidence of colonic polyps was reported in 51.2% of patients, including adenomas in 33.3% among the colitis patients with median follow up duration of 12 months. The incidence of adenoma polyps 12 months after the colitis event was significantly higher compared to the control group without colitis based on the time-to-event analysis (p=0.041). Conclusion: At a median follow up of 12 months after their initial colitis diagnosis, 51.2% of the patients had new incidence of colonic polyps, including a third with adenoma, at a significantly higher incidence than the control group without colitis. Studies with larger sample sizes are needed to further define the long-term impact of colitis and its treatments on colon health and to refine recommendations for surveillance of colonic adenomas and colorectal cancer.

Immune checkpoint inhibitor gastritis is often associated with concomitant enterocolitis, which impacts the clinical course.

Gastrointestinal immune-related adverse events are frequently caused by immune checkpoint inhibitors (ICIs) and often require interruption of cancer treatment. Compared with ICI colitis and enteritis, limited information exists about ICI gastritis. This study characterized clinical features and treatment outcomes of ICI gastritis. Consecutive cancer patients who received ICIs and underwent endoscopy with gastric biopsies while on ICIs from 2011 to 2021 were retrospectively assessed. Specific histopathologic features identified ICI gastritis. Of 6450 ICI-treated patients, 162 (2.5%) underwent endoscopy with gastric biopsies. ICI gastritis was identified in 54 (33%) biopsied patients; 38 (70%) had concurrent ICI enteritis/colitis and 16 (30%) had isolated ICI gastritis. Dyspepsia (38%) and bloating (25%) were the most frequent symptoms of isolated ICI gastritis. Compared with patients with concomitant enteritis/colitis, patients with isolated gastritis were less likely to have diarrhea (13% vs 68%; p<.001) or abdominal pain (19% vs 47%; p=.07). Patients with isolated ICI gastritis less frequently required glucocorticoids (69% vs 92%; p=.04) and had lower incidence of ICI hold/withdrawal (13% vs 42%; p=.06). There was no association between severity or extent of luminal inflammation and antitumor response (p=.85 and p=.44, respectively). Endoscopically, gastric mucosa appeared normal in 11 (20%) patients with biopsy-proven ICI gastritis. ICI gastritis may present alone or more commonly with concurrent enteritis/colitis, which may differentiate its clinical course. Gastric biopsies are required to diagnose a substantial minority of endoscopically normal, clinically significant cases. Most patients with isolated gastritis can continue ICI therapy uninterrupted, but a notable proportion require glucocorticoids. Immune checkpoint inhibitors are effective anticancer treatments, but can cause inflammatory toxicities, including of the stomach (gastritis), intestine, and colon. Limited information is available on gastritis triggered by these agents. Adult patients with cancer who were treated with immune checkpoint inhibitors and had an upper gastrointestinal endoscopy with biopsies of the stomach were examined. More than two-thirds (70%) of people with checkpoint inhibitor gastritis also had inflammatory changes of the small intestine and/or colon. Compared with patients with isolated checkpoint gastritis, the subgroup with concomitant enteritis/colitis more frequently had abdominal pain, diarrhea, needed steroids, and/or needed to pause or stop antitumor therapy.

S218 Prevalence and Outcomes of Immune Checkpoint Inhibitor (ICI) Associated Colitis: A Population-Based Cohort Study

Introduction: Immune checkpoint inhibitors (ICIs) can trigger an overactivation of the immune system, resulting in an autoimmune-like process in various organ systems. Involvement of the gastrointestinal (GI) tract has been frequently reported in literature. The primary aim of this study was to evaluate the prevalence and disease outcomes of ICI colitis. Methods: A retrospective cohort study was conducted using TriNetX, a multi-institutional database of more than 70 million patients from 49 healthcare organizations in the USA. ICI colitis cohort included patients on Nivolumab, Ipilimumab, Pembrolizumab, Atezolizumb, Durvalumab, Avelumab or Cemiplimab who developed colitis within 1 year of initiation of ICI. Patients with inflammatory bowel disease (IBD), GI infections and intestinal ischemia were excluded from the study. Disease outcomes that were evaluated included hospitalization, oral/IV steroid use, biologic use and mortality within 3 months of ICI colitis. Disease outcomes between patients on CTLA-4 inhibitor and PD-1 inhibitor; and CTLA-4 inhibitor and PD-L1 inhibitor were compared after 1:1 propensity matching for age, gender, race and ethnicity and reported as adjusted Odds Ratios (aOR) with 95% confidence intervals (CIs). Results: Out of 57,067 patients on ICIs, 4128 (7.23%) patients developed ICI colitis (mean age 64 ± 12, male 56%, Caucasian 77%). The prevalence of ICI colitis was 5.9% in Pembrolizumab, 15.5% in Ipilimumab, 5.5% in Nivolumab, 3% in Durvalumab, 5.8% in Atezolizumab, 3% in Cemiplimab and 2.8% in Avelumab. 34% required hospitalization, 44% required oral steroids, 6.6% required IV steroids, 6% required a biologic agent and 0.2% required colectomy (Figure). 90-day mortality was observed in 15% of patients. Patients with ICI colitis from CTLA-4 inhibitors were more likely to require oral steroids [aOR 1.62, 95% CI 1.33-1.98], IV steroids [1.54, 1.15-2.07] and infliximab [OR 2.18, 1.62-2.91] compared to those on PD-1 inhibitors. Patients with ICI colitis from CTLA-4 inhibitors were also more likely to require oral steroids [aOR 3.33, 95% CI 2.36-4.69], IV steroids [2.45, 1.49-4.02] and infliximab [OR 7.35, 3.73-14.50] compared to those on PD-L1 inhibitors (Table). Conclusion: Approximately 50% of patients with ICI colitis require either PO or IV steroids. Patients on CTLA-4 inhibitors are more likely to have a worse disease course compared to patients on PD-1 or PD-L1 inhibitors.Figure 1.: Clinical outcomes of the patients with ICI colitis Oral steroids: Prednisone or Budesonide; IV steroids: Methylprednisolone; Biologic: Infliximab or Vedolizumab; Surgical intervention: total or subtotal colectomy Table 1. - Comparison of the clinical outcomes between patients that developed Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitor colitis vs Programmed death-ligand 1 (PD-L1) inhibitor associated colitis and CTLA-4 inhibitor colitis vs Programmed cell death protein 1 (PD-1) inhibitor colitis Clinical Outcomes CTLA-4 vs PD-L1 (OR, CI) CTLA-4 vs PD-1 (OR, CI) Oral steroids 3.333 (2.368-4.693) 1.626 (1.334-1.982) IV steroids 2.450 (1.491-4.025) 1.546 (1.154-2.071) Infliximab 7.355 (3.73, 14.502) 2.175 (1.625-2.912) Hospitalization 1.256 (0.73-1.621) 1.096 (0.916-1.31) ICU care 1.00 (0.626, 1.596) 0.972 (0.697-1.354) CTLA-4 inhibitor: Ipilimumab; PD-1 inhibitor: pembrolizumab, and nivolumab; PD-L1 inhibitor: avelumab, atezolizumab and durvalumab.

S726 Fecal Transplantation Improved Patients’ Reported Outcome After Immune Checkpoint Inhibitor Colitis

Introduction: Immune checkpoint inhibitors (ICIs) have become standard treatment for cancers poorly responsive to traditional chemotherapy. The most common GI toxicity of this class of drugs is ICIs colitis (IMC) associated with difficulty to treat chronic diarrhea and risk of fatality. We have previously demonstrated that fecal microbiota transplantation (FMT) was effective in the treatment of a small number of refractory cases suggesting the gut microbiome is involved in the pathogenesis of ICIs colitis. Further large studies are needed to determine its efficacy. Methods: The present study summarizes our experience with FMT treatment of 37 patients with refractory ICIs colitis. We measured the efficacy of FMT and patients’ reported outcome (PRO) via established MD Anderson Symptom Inventory (MDASI). Among them, 9 patients had concurrent CDI as well at the time of diagnosis. (Table) Results: Thirty-seven patients included in our study, with a median age of 59 years and mostly had genitourinary cancers (35.1%) followed by melanoma (27.0%). Most patients had a peak CTCAE diarrhea grade ≥ 3 (91.9%) and colitis grade ≥ 2 (89.1%). Ulcerous (18, 48.6%) and non-ulcerous (12, 32.4%) inflammation was predominant endoscopic findings. 36 (97.3%) patients received corticosteroids, and 33 (89.1%) received add-on infliximab or vedolizumab. IMC symptom response was 83.7% after FMT with median time to response of 5 days. The rate of complications is 16.2% at 7 days and 5.4% at 30 days, and mostly were transient and mild. Response rate among 28 patients without concurrent CDI was 85.7%. Thirty-five (94.6%) patients demonstrated colitis remission at the last follow up. On the PRO analysis, we observed a favorable trend of significant patient-reported symptom reduction on diarrhea during 12 weeks after FMT, along with improved daily physical functioning on working. (Figure) Conclusion: Evidence is accumulating to suggest that efficacy and prevention of ICI related toxicities is dependent upon a healthy diverse microbiome. In the present study, we have shown that FMT achieved 83.7% success rate in patients with IMC with a favorable safety profile. FMT could become a preferred treatment option for the IMC in the future practice.Figure 1.: Patients Reported Outcome Summary Table 1. - Characteristic before FMT No. (%) (n=37) Concurrent CDI# 9 (24.3%) Highest grade of diarrhea of initial IMC onset – no. (%) 1 or 2 3 (8.1%) 3 or 4 34 (91.9%) Highest grade of colitis of initial IMC onset – no. (%) 1 4 (10.8%) 2- 4 33 (89.2%) Initial endoscopic findings – no (%), n=36 Ulcers 18 (48.6%) Non-ulcer inflammation 12 (32.4%) Normal 6 (16.2%) Hospitalizations – no. (%) 29 (78.3%) Median duration of hospitalization – days (IQR) 8 (5-13) Treatment of GI adverse events – no. (%) Steroid 36 (97.3%) Infliximab/vedolizumab added 33 (89.1%) FMT characteristic and outcome Symptom improvement after FMT, all patients – no (%) 31 (83.7%) Symptom improvement after FMT (no concurrent CDI, n=28) – no (%) 24 (85.7%) Median time from FMT to symptom improvement– days (IQR), n=37 5 (2-10) FMT-related complications within 7 days –no (%) 6 (16.2%) FMT-related complications within 30 days –no (%) 2 (5.4%) Colitis status at the end of the study period Clinical remission – no (%) 35 (94.6%) Persistent symptoms – no (%) 2 (5.4%)

S2211 A Rare Case of Refractory Immune Checkpoint Inhibitor Colitis Complicated by Concurrent Clostridioides difficile Infection

S2211 A Rare Case of Refractory Immune Checkpoint Inhibitor Colitis Complicated by Concurrent Clostridioides difficile Infection

S903 The Impact of Immunosuppression for Immune Checkpoint Inhibitor Colitis on Cancer Outcome

Introduction: Immune checkpoint inhibitors are becoming a staple in the management of certain types of cancer. However, they may give rise to immune-related adverse events (irAEs). In particular, gastrointestinal irAEs may sometimes necessitate extended periods of steroid use and initiation of biologic agents. In this study, we aim to explore the impact of immunosuppression use and duration on cancer progression and progression-free survival (PFS). Methods: This is a single center retrospective review in patients taking ICIs who developed gastrointestinal irAEs within one year of ICI initiation. The study window for data collection ranged from May 2011 to June 2020. Data was analyzed using IBM SPSS Statistics 26; univariate logistic regression was used to explore the relationship between immunosuppression and cancer progression and COX Hazard analysis was conducted to evaluate progression-free survival. 30 days was used as the cut-off to differentiate between short and long-term steroid use for analysis. Results: 113 patients were included in this study, 49 of whom did not receive any immunosuppression. All patients developed IMDC, but 16 patients had no colitis symptoms. 23 patients received a short duration of steroids while 41 patients received immunosuppression for longer than 30 days. The development of colitis was associated with less cancer progression by the fourth staging (p< 0.05) within the study window while immunosuppression for colitis correlated with less progression by third staging (p< 0.05). The multivariate COX analysis found that durations of steroid use (with or without concurrent biologic use) less than 30 days were associated with better progression-free survival (PFS;p=0.048). The number of ICI infusions also seemed to correlate with better PFS (p=0.089). Conclusion: The impact of immunosuppressive treatment on cancer outcomes has not been well studied. This study found that durations of steroid treatment less than 30 days for ICI colitis showed significantly less cancer progression within one year of ICI treatment, supporting emerging evidence that prolonged steroid use may interfere with immunotherapy efficacy. We also found that the development of colitis and the use of immunosuppression was associated with less cancer progression with a year. This study supports the benefit of GI irAE on cancer outcome and raises concern for the safety of long-term immunosuppression for managing ICI GI toxicities highlighting the need for more extensive research into this particular area.

1667P Multiplexed spatial analysis by imaging mass cytometry to immunologically characterize checkpoint inhibitor colitis

Immune checkpoint inhibitor (ICI) colitis is among the most prevalent immune-related adverse events (irAEs) of immune checkpoint blockade (ICB). Deeper pathophysiological understanding can contribute to evidence-based management of ICI colitis. While single-cell RNA sequencing studies lack tissue architectural insight, we used imaging mass cytometry (IMC) to study ICI colitis spatially in high immunological detail.

Mesalamine and cholestyramine for immune checkpoint inhibitor-mediated diarrhea and colitis.

Immune checkpoint inhibitors (ICI) are effective against various malignancies. However, adverse events including diarrhea and colitis can lead to significant morbidity and mortality. Recommendations for the management of ICI mediateddiarrhea and colitisinclude steroids and biologics. Given their associated risks, this study evaluated the role of thenon-immunosuppressive agents, mesalamine and or cholestyramine. This is a retrospective, descriptive, single-center study of adults who developed ICI diarrhea and colitis between 2010 and 2020 at MD Anderson Cancer Center. Clinical data and outcomes were compared between those treated with the non-immunosuppressive therapies mesalamine and/or cholestyramine alone versus those who received additional immunosuppression with steroids and biologics. Our sample comprised 66 patients wherein, the mean age was 63years, 71% were males, and 97% had stage III/IV cancers. Fourteen patients were treated successfully with non-immunosuppressive therapy. They had grade 1-3 diarrhea and 1-2 colitis with no difference inthe rate of histologic colitis compared to those who received immunosuppressive therapy. They had less CTLA-4 inhibitor-based therapy (36% vs. 73%, p = 0.034), delayed onset of symptoms (159 vs. 64days, p = 0.011), lower fecal calprotectin levels (56 vs. 234, p = 0.012) and were more likely to resume ICI therapy (64% vs. 25%, p = 0.006). Mesalamine and/or cholestyramine may be effective for mild ICI diarrhea and colitis among patients with delayed symptom onset with lower colonic inflammatory burden. Prospective studies randomizing patients with mild colitis between mesalamine/cholestyramine and immunosuppressive treatment are warranted to assess their efficacy and safety.