Workup and Management of Immune-Mediated Colitis in Patients Treated with Immune Checkpoint Inhibitors

Singh, Bhavana; Marshall, John L.; He, Aiwu Ruth

doi:10.1634/theoncologist.2018-0304

Cited by 14 publications

(16 citation statements)

References 39 publications

(49 reference statements)

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“…Currently, oncologic guidelines for management of IMDC are based primarily on clinical symptoms. 5 6 Common Terminology Criteria for Adverse Events (CTCAE) grade 2 irAE should prompt initiation of corticosteroid therapy. Grade 3 or higher irAEs indicate a need for hospitalization and corticosteroid-sparing therapy, namely infliximab and vedolizumab, until clinical remission has been achieved.…”

Section: Introductionmentioning

confidence: 99%

Fecal calprotectin concentration to assess endoscopic and histologic remission in patients with cancer with immune-mediated diarrhea and colitis

Zou

Wang

Glitza

et al. 2021

J Immunother Cancer

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BackgroundImmune-mediated diarrhea and colitis (IMDC) is currently diagnosed and monitored by evaluating clinical symptoms. Deep remission is determined by endoscopic and histologic evaluation of the disease process. However, repeating these invasive procedures frequently can become cumbersome. We sought to assess the role of fecal calprotectin (FC) concentration as a non-invasive biomarker of endoscopic or histologic remission.MethodsWe performed a retrospective study of patients with IMDC who were tested for FC at IMDC onset and after IMDC treatment between June 2016 and March 2020. Patient demographics, clinical variables, and FC data were collected and analyzed to determine the optimal cut-off FC concentration to predict endoscopic and histologic remission.ResultsOur sample comprised 77 patients with a median age of 62 years; 66% were male and 94% were Caucasian. Sixty-five patients (84%) achieved clinical remission, 46 (60%) achieved endoscopic remission, and 24 (31%) achieved histologic remission after IMDC treatment. FC concentrations decreased from the time of IMDC onset to the end of treatment (p<0.001). High FC concentrations were associated with evident endoscopic inflammation (p=0.003) and acute/chronic active colitis (p=0.025) which positively correlated with the Mayo Endoscopic Subscore (r=0.615, p=0.001) at the time of IMDC onset. In patients who achieved endoscopic remission after treatment, a significantly lower FC concentration was observed at IMDC onset (p=0.006) and after treatment (p<0.001) compared with those without endoscopic remission. The cut-off FC concentration to predict endoscopic remission was ≤116 μg/g and for histologic remission ≤80 μg/g; these cut-offs had optimal specificity (94% and 85%, respectively) and positive predictive value (0.91 and 0.38, respectively).ConclusionsFC concentration may serve as a non-invasive biomarker to predict endoscopic and histologic remission in patients receiving treatment for IMDC, minimizing the need for frequent invasive endoscopies. Future prospective studies are needed to provide further insight on the role of this marker in disease surveillance.

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Section: Introductionmentioning

confidence: 99%

Fecal calprotectin concentration to assess endoscopic and histologic remission in patients with cancer with immune-mediated diarrhea and colitis

Zou

Wang

Glitza

et al. 2021

J Immunother Cancer

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“…For grade 3-4, hospital admission is recommended, and treatment includes intravenous high-dose corticosteroids, followed by a taper. Checkpoint inhibitor therapy must be discontinued permanently [12]. Early recognition of these toxicities is crucial in minimizing the impact of these complications on planned antineoplastic therapy.…”

Section: Discussionmentioning

confidence: 99%

Immune Checkpoint Inhibitor-Induced Acute Pancreatitis and Colitis

Pagan

Arroyo-Martinez

Tandon

et al. 2020

Cureus

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Given the promising response of immune checkpoint inhibitors (ICPIs) in treating advanced malignancies, their use in clinical practice is on the rise. ICPIs are associated with a wide spectrum of immune-related adverse events (irAEs). The reported side effects of therapy can be severe enough to require interruption or withdrawal. We are presenting a case of a checkpoint inhibitor-induced acute pancreatitis and colitis, treated with high-dose steroids. This case highlights the need for all physicians to be aware of the different presentations of irAEs from checkpoint inhibitors to provide the correct diagnosis and management.

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“…Immunemediated diarrhea and colitis (IMDC), the second most common irAE, limits the use of ICIs. 5 The incidence and severity of IMDC vary depending on the ICI regimen. Severe forms are attributed to anti-CTLA-4-based regimens, 6 and clinical symptoms range from self-limited diarrhea to severe life-threatening diarrhea, bleeding, colonic dilatation, and bowel perforation.…”

Section: Introductionmentioning

confidence: 99%

Association of Chronic Immune-Mediated Diarrhea and Colitis With Favorable Cancer Response

Zou

Abu-Sbeih

et al. 2021

Journal of the National Comprehensive Cancer Network

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Background: Immune-mediated diarrhea and colitis (IMDC) is a common immune-related adverse effect related to immune checkpoint inhibitors. We aimed to identify risk factors for chronic IMDC and its prognostic value in cancer outcomes. Methods: We retrospectively collected data on patients with a diagnosis of IMDC between January 2018 and October 2019 and grouped them based on disease duration into acute (≤3 months) and chronic (>3 months) categories. A logistic regression model and the Kaplan-Meier method with log-rank tests were used for biostatistical analysis. Results: In our sample of 88 patients, 43 were in the chronic group and 45 were in the acute group. Genitourinary cancer and melanoma accounted for 70% of malignancies. PD-1/L1 monotherapy (52%) was the more frequently used regimen. We showed that chronic IMDC was associated with proton pump inhibitor use (odds ratio [OR], 3.96; P=.026), long duration of IMDC symptoms (OR, 1.05; P<.001) and hospitalization (OR, 1.07; P=.043), a histologic feature of chronic active colitis (OR, 4.8; P=.025) or microscopic colitis (OR, 5.0; P=.045), and delayed introduction of selective immunosuppressive therapy (infliximab/vedolizumab; OR, 1.06; P=.047). Chronic IMDC also reflected a better cancer response to immune checkpoint inhibitors (30% vs 51%; P=.002) and was accompanied by improved overall survival (P=.035). Similarly, higher doses of selective immunosuppressive therapy were associated with better overall survival (P=.018). Conclusions: Chronic IMDC can develop among patients with a more aggressive disease course and chronic features on colon histology. It likely reflects a prolonged immune checkpoint inhibitor effect and is associated with better cancer outcome and overall survival.

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Workup and Management of Immune-Mediated Colitis in Patients Treated with Immune Checkpoint Inhibitors

Cited by 14 publications

References 39 publications

Fecal calprotectin concentration to assess endoscopic and histologic remission in patients with cancer with immune-mediated diarrhea and colitis

Fecal calprotectin concentration to assess endoscopic and histologic remission in patients with cancer with immune-mediated diarrhea and colitis

Immune Checkpoint Inhibitor-Induced Acute Pancreatitis and Colitis

Association of Chronic Immune-Mediated Diarrhea and Colitis With Favorable Cancer Response

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