Endoscopic and Histologic Features of Immune Checkpoint Inhibitor-Related Colitis

Wang, Yinghong; Abu-Sbeih, Hamzah; Mao, Emily; Ali, Noman; Qiao, Wei; Trinh, Van Anh; Zobniw, Chrystia M.; Johnson, Daniel; Samdani, Rashmi; Lum, Phillip; Shuttlesworth, Gladis; Blechacz, Boris; Bresalier, Robert S.; Miller, Ethan; Thirumurthi, Selvi; Richards, David M.; Raju, Gottumukkala S.; Stroehlein, John R.; Diab, Adi

doi:10.1093/ibd/izy104

Cited by 200 publications

(219 citation statements)

References 19 publications

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“…Hypoalbuminemia may result from enteric ulcerations that are associated with more severe GEC. [34][35][36] The difference in relative lymphopenia we observed, without significant difference in absolute lymphopenia, may indicate increased neutrophilic production, driven perhaps in part by elevated interleukin-17 levels 40 but more likely by multiple cytokines generated in response to gastrointestinal mucosal compromise and subsequent immune activation by microbial products. Lower LDH may suggest that CPI-related GEC which requires hospitalization and second-line immunosuppression is actually a positive prognostic factor for oncologic response.…”

Section: F I G U R Ementioning

confidence: 78%

“…Several recent investigations have suggested serologic markers for severe CPI-related GEC development. [33][34][35] In particular, high-risk endoscopic findings including significant ulceration have been associated with the need for second-line immunosuppression. 36 In our cohort, second-line immunosuppression was administered at a 50.0% frequency, a rate higher than the 22.5% rate in previous reports, likely reflecting the overall higher acuity of this cohort as admission to a tertiary care hospital was a requirement for study inclusion.…”

Section: Use Of Second-line Immunosuppression P-valuementioning

confidence: 99%

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Colitis after checkpoint blockade: A retrospective cohort study of melanoma patients requiring admission for symptom control

et al. 2019

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Background Immune checkpoint inhibitors (CPIs) have revolutionized oncologic therapy but can lead to immune‐related adverse events (irAEs). Corticosteroids are first‐line treatment with escalation to biologic immunosuppression in refractory cases. CPI‐related gastroenterocolitis (GEC) affects 20%‐50% of patients receiving CPIs and can carry significant morbidity and mortality. Severe CPI‐related GEC is not well‐described. We present the clinical characterization of all CPI‐related GEC requiring admission at a single institution. Methods Clinical, laboratory, radiographic, and endoscopic data were extracted from charts of all melanoma patients ≥18 years of age admitted to one institution for CPI‐related GEC, from February 5, 2011 to December 13, 2016. Patients were followed until December 31, 2017 for further admissions. Survival, outcomes, and pharmaceutical‐use analyses were performed. Results Median time‐to‐admission from initial CPI exposure was 73.5 days. Median length of stay was 4.5 days. About 50.0% required second‐line immunosuppression. Readmission for recrudescence occurred in 33.3%. Common Terminology Criteria for Adverse Events (CTCAE) grade was not significantly associated with outcomes. Hypoalbuminemia ( P = 0.005), relative lymphopenia ( P = 0.027), and decreased lactate dehydrogenase ( P = 0.026) were associated with second‐line immunosuppression. There was no difference in progression‐free survival (PFS) or OS ( P = 0.367, 0.400) for second‐line immunosuppression. Subgroup analysis showed that early corticosteroid administration ( P = 0.045) was associated with decreased PFS. Conclusions Severe CPI‐related GEC typically manifests within 3 months of immunotherapy exposure. Rates of second‐line immunosuppression and readmission for recrudescence were high. CTCAE grade did not capture the degree of severity in our cohort. Second‐line immunosuppression was not associated with poorer oncologic outcomes; however, early corticosteroid exposure was associated with decreased PFS. Further investigation is warranted.

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Section: F I G U R Ementioning

confidence: 78%

Section: Use Of Second-line Immunosuppression P-valuementioning

confidence: 99%

Colitis after checkpoint blockade: A retrospective cohort study of melanoma patients requiring admission for symptom control

et al. 2019

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“…In another retrospective series, which included 117 patients treated with ICI who developed diarrhea, a steroid duration >30 days was associated with higher rates of infection compared with a shorter duration of steroid use with or without infliximab . In a retrospective series of the endoscopic and histologic features of ICI‐induced colitis, patients with ulcerations on colonoscopy were more likely to have steroid‐refractory colitis …”

Section: Checkpoint Inhibitorsmentioning

confidence: 99%

“…44 In a retrospective series of the endoscopic and histologic features of ICI-induced colitis, patients with ulcerations on colonoscopy were more likely to have steroid-refractory colitis. 45 Vedolizumab, an anti-integrin α4β7 antibody with gut-specific effects, has been investigated for patients with steroid-dependent or refractory ICI-induced colitis. For instance, a retrospective series of 28 patients who were treated with vedolizumab for immune-related enterocolitis that was refractory to steroids and/or infliximab described sustained clinical remission in 24 of 28 patients after a median of 3 doses of vedolizumab.…”

Section: Dermatologic Toxicitymentioning

confidence: 99%

A review of cancer immunotherapy toxicity

Kennedy

Salama

2020

CA A Cancer J Clinicians

988

699

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Cancer immunotherapies, including checkpoint inhibitors and adoptive cell therapy, manipulate the immune system to recognize and attack cancer cells. These therapies have the potential to induce durable responses in multiple solid and hematologic malignancies and thus have transformed treatment algorithms for numerous tumor types. Cancer immunotherapies lead to unique toxicity profiles distinct from the toxicities of other cancer therapies, depending on their mechanism of action. These toxicities often require specific management, which can include steroids and immune‐modulating therapy and for which consensus guidelines have been published. This review will focus on the toxicities of checkpoint inhibitors and chimeric antigen receptor T cells, including pathophysiology, diagnosis, and management.

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“…ICI-induced diarrhea occurs in 10-30% of patients and <10% of patients develop severe colitis. [3][4][5][6][7]9 In the present cases series, we carried out a retrospective analysis of patients with ICI-induced diarrhea to clarify the clinicopathological characteristics of the disease.…”

Section: Mmune Checkpoint Inhibitors (Ici) Have Beenmentioning

confidence: 99%

Immune checkpoint inhibitor‐induced diarrhea: Clinicopathological study of 11 patients

Yanai

Nakamura

Kawasaki

et al. 2019

Digestive Endoscopy

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We reviewed the records of patients with immune checkpoint inhibitor (ICI)-induced diarrhea during 2015 to 2019. ICI included nivolumab and ipilimumab. There were 11 patients with ICIinduced diarrhea aged 46-81 years (median, 63 years). On colonoscopy, four patients appeared normal, whereas loss of vascularity, erythema, granularity, erosions or ulcerations apparently mimicking ulcerative colitis were found in seven patients. Those seven patients had acute inflammation, cryptitis, crypt abscess and apoptosis, suggestive of ICI-induced colitis. Five of the seven patients were treated with prednisolone, two of whom were resistant to prednisolone and required infliximab. In contrast, none of the four patients without ICI-induced colitis required further treatment. Our observations suggest that diversity exists in the clinical, endoscopic and histological severity of patients with ICIinduced diarrhea. Colonoscopy together with biopsy is inevitable for the diagnosis of ICI-induced colitis, which requires intensive treatment.

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Endoscopic and Histologic Features of Immune Checkpoint Inhibitor-Related Colitis

Abstract: 10.1093/ibd/izy104_video1izy104.video15808053084001.

Cited by 200 publications

References 19 publications

Colitis after checkpoint blockade: A retrospective cohort study of melanoma patients requiring admission for symptom control

Colitis after checkpoint blockade: A retrospective cohort study of melanoma patients requiring admission for symptom control

A review of cancer immunotherapy toxicity

Immune checkpoint inhibitor‐induced diarrhea: Clinicopathological study of 11 patients

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