668 Immune Checkpoint Inhibitor Related Colitis (ICI-Colitis) in Patients With Preexisting Inflammatory Bowel Disease or Microscopic Colitis

Abstract Background Immune checkpoint inhibitor therapy has significantly improved the outcomes of various advanced malignancies that were deemed unruly prior to its invention. Immune-mediated diarrhea and enterocolitis are among the most frequently encountered adverse events of immune checkpoint inhibitor therapy. Given the increasing use of these therapies in the treatment of an ever-growing number of malignancies, providing appropriate treatment for such adverse effects has become crucial. Methods In this review, we summarize the current body of evidence concerning the management of immune-mediated diarrhea and enterocolitis. Additionally, management of immune-mediated diarrhea and enterocolitis is likened to that of inflammatory bowel disease, given the resemblance between both entities in pathogenesis and clinical features. Reviewing the literature raised several points regarding this devastating toxicity that still need further investigation by future efforts. Results Endoscopic and histologic evaluation is pivotal in the assessment of immune-mediated diarrhea and enterocolitis and provides vital information regarding the severity of the disease to guide treatment. Corticosteroids are the main therapy for immune-mediated diarrhea and enterocolitis, with infliximab and vedolizumab as second-line agents. Recently, fecal microbiota transplantation has emerged as a treatment option for immune-mediated diarrhea and enterocolitis that is refractory to corticosteroids. Restarting immune checkpoint inhibitor therapy after resolution of immune-mediated diarrhea and enterocolitis carries a risk of recurrence that is mostly controllable with current immune-suppressive treatment. Conclusions Lastly, we propose a management algorithm for immune-mediated diarrhea and enterocolitis. Prospective research, preferably as collaborative efforts from oncology and gastroenterology specialists, is needed to refine the management of immune-mediated diarrhea and enterocolitis.

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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

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2021-002567 ◽

2021 ◽

Vol 9 (6) ◽

pp. e002567

Author(s):

Joseph Sleiman ◽

Wei Wei ◽

Ravi Shah ◽

Muhammad Salman Faisal ◽

Jessica Philpott ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Overall Survival ◽

Bowel Disease ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitor ◽

Checkpoint Inhibitor ◽

Matched Cohort ◽

Patients With Cancer ◽

History Of ◽

Inflammatory Bowel

Background and aimsThe risk of use of immune-mediated diarrhea and colitis (imDC) in patients with preexisting inflammatory bowel disease (IBD) is not fully understood. We report the incidence of imDC in these patients, and compare with a matched cohort of patients with cancer and without IBD.MethodsPatients with IBD from a tertiary center cancer registry who underwent immune checkpoint inhibitor (ICI) therapy from 2011 to 2019 were identified. A 1:5 matched cohort of patients with and without a history of IBD was created, based on age, ICI therapy, and cancer type. Demographic data, clinical history of IBD, cancer, ICI agent, imDC events after ICI therapy, and overall survival were analyzed. Overall survival and time-to-imDC (TTimDC) were estimated by Kaplan-Meier and multivariate Cox proportional-hazards models.ResultsFrom a retrospective cohort of 3900 patients who received ICI therapy, 30 patients with IBD were matched with 150 patients without a history of IBD. Most patients received PD-1/PD-L1 inhibitor monotherapy (154/180, 85.6%). Individuals with preexisting IBD showed significantly shorter TTimDC than those in the non-IBD group (1-year imDC-free rate 67% vs 93%; HR 7.59, 95% CI 3.00 to 19.15, p<0.0001). Eleven (36%) from the IBD cohort experienced imDC events; none led to life-threatening conditions needing surgical interventions or death. Corticosteroids or biologics were needed in 8/11 (73%) patients, and discontinuation of therapy improved imDC in the remaining three. Half of patients required hospitalization. In contrast, no significant difference in overall survival was observed between IBD and non-IBD cohorts (HR 0.89, 95% CI 0.54 to 1.48). Both groups had overall comparable rates of other non-imDC immune-related adverse events.ConclusionPatients with preexisting IBD had worse time-to-imDC than non-IBD matched controls, yet did not exhibit worse overall survival. While close monitoring of patients with preexisting IBD is warranted while on immunotherapy, this comorbidity should not preclude ICI therapy if clinically required.

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Meaningful Symptoms of Immune Checkpoint Inhibitor Therapy–Related Gastrointestinal Adverse Events in Patients With Inflammatory Bowel Disease

Journal of Clinical Oncology ◽

10.1200/jco.20.00033 ◽

2020 ◽

Vol 38 (15) ◽

pp. 1748-1749

Author(s):

Yuji Inagaki ◽

Kouji Azuma ◽

Yukihiro Nakamura ◽

Shunichi Kouno ◽

Yoshinobu Matsuda ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Adverse Events ◽

Bowel Disease ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitor ◽

Checkpoint Inhibitor ◽

Inhibitor Therapy ◽

Checkpoint Inhibitor Therapy ◽

Inflammatory Bowel ◽

Gastrointestinal Adverse Events

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Safety of Immune Checkpoint Inhibitors in Patients With Pre-Existing Inflammatory Bowel Disease and Microscopic Colitis

JCO Oncology Practice ◽

10.1200/jop.19.00672 ◽

2020 ◽

Vol 16 (9) ◽

pp. e933-e942 ◽

Cited By ~ 2

Author(s):

Shilpa Grover ◽

Alex B. Ruan ◽

Padmavathi Srivoleti ◽

Anita Giobbie-Hurder ◽

Marta Braschi-Amirfarzan ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Cytotoxic T Lymphocyte ◽

Checkpoint Inhibitors ◽

Outcome Data ◽

Microscopic Colitis ◽

Patients With Cancer ◽

Inflammatory Bowel

PURPOSE: Enterocolitis is among the leading adverse events associated with immune checkpoint inhibitors (ICIs). There are limited retrospective data regarding the safety of ICIs in patients with inflammatory bowel disease (IBD; ulcerative colitis, Crohn’s disease) because they have been generally excluded from clinical trials testing ICIs. Furthermore, there are no outcome data available in patients with microscopic colitis, a leading cause of chronic diarrhea. We aimed to study the safety of ICIs in patients with cancer with pre-existing IBD or microscopic colitis. METHODS: We retrospectively reviewed the records of patients with cancer treated at our institution who received at least 1 dose of either a programmed cell death-1 (PD-1)/ PD-1 ligand inhibitor, cytotoxic T-lymphocyte-associated antigen 4 inhibitor, or both between 2011 and 2018. We identified patients with pre-existing IBD or microscopic colitis. RESULTS: Of 548 patients with solid tumor treated with an ICI, we identified 25 with pre-existing colitis (21 IBD; 4 microscopic colitis). An enterocolitis flare occurred in 7 patients (28%): 3 of 4 patients (75%) with microscopic colitis and 4 of 21 (19%) with IBD. All were treated with systemic corticosteroids, 2 required an anti–tumor necrosis factor agent, and one required an anti-integrin agent and colectomy for treatment of refractory colitis. ICI therapy was discontinued in all patients who experienced an enterocolitis flare. CONCLUSION: In our cohort, exacerbation of enterocolitis occurred in a notable percentage of patients with IBD and a majority of patients with microscopic colitis, leading to discontinuation of ICIs. Although these data suggest that patients with cancer with pre-existing IBD/microscopic colitis may be treated with ICIs, additional studies are needed to validate our results.

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Su1189 SAFETY OF IMMUNE CHECKPOINT INHIBITORS IN PATIENTS WITH PREEXISTING INFLAMMATORY BOWEL DISEASE AND MICROSCOPIC COLITIS

Gastroenterology ◽

10.1016/s0016-5085(20)32037-0 ◽

2020 ◽

Vol 158 (6) ◽

pp. S-537

Author(s):

Shilpa Grover ◽

Alex Ruan ◽

Padma Srivoleti ◽

Anita Giobbie-Hurder ◽

Marta Braschi-Amirfarzan ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Microscopic Colitis ◽

Inflammatory Bowel

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Faculty Opinions recommendation of Checkpoint Inhibitor Colitis Shows Drug-Specific Differences in Immune Cell Reaction That Overlap With Inflammatory Bowel Disease and Predict Response to Colitis Therapy.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.739510767.793584679 ◽

2021 ◽

Author(s):

Noam Harpaz ◽

Alexandros D. Polydorides

Keyword(s):

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Immune Cell ◽

Checkpoint Inhibitor ◽

Cell Reaction ◽

Inflammatory Bowel

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Immune Checkpoint Inhibitor Therapy in Patients With Preexisting Inflammatory Bowel Disease

Journal of Clinical Oncology ◽

10.1200/jco.19.01674 ◽

2020 ◽

Vol 38 (6) ◽

pp. 576-583 ◽

Cited By ~ 23

Author(s):

Hamzah Abu-Sbeih ◽

David M. Faleck ◽

Biagio Ricciuti ◽

Robin B. Mendelsohn ◽

Abdul R. Naqash ◽

...

Keyword(s):

Adverse Events ◽

T Lymphocyte ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitor ◽

Cytotoxic T Lymphocyte ◽

Checkpoint Inhibitor ◽

Checkpoint Inhibitors ◽

Inhibitor Therapy ◽

Checkpoint Inhibitor Therapy ◽

Inflammatory Bowel

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 METHODS We 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. RESULTS Of 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.

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