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Severe Inflammatory Colitis Related to Encorafenib and Binimetinib following Immune Checkpoint Inhibitor Therapy.

ABSTRACT: Encorafenib, a BRAF kinase inhibitor, in combination with binimetinib, a selective MEK inhibitor have known gastrointestinal adverse events; however, adverse colitis events have not been well studied. We report a case series of 4 patients with melanoma who developed inflammatory colitis after BRAF and MEK inhibition with encorafenib and binimetinib, respectively. In the setting of immune checkpoint inhibitor use, BRAF and MEK inhibitors can cause significant inflammatory colitis with endoscopic patterns of predominant right colon ulcerations. It can lead to significant morbidity and frequent interruption of cancer treatment. Early recognition and prompt intervention are critical to improving patient outcomes.

SUBMITTER: Issac AG

PROVIDER: S-EPMC9247533 | biostudies-literature | 2022 May-Aug

REPOSITORIES: biostudies-literature

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Severe Inflammatory Colitis Related to Encorafenib and Binimetinib following Immune Checkpoint Inhibitor Therapy.

Issac Aaron G AG Szafron David D Wei Dongguang D McQuade Jennifer L JL Wang Yinghong Y

Case reports in gastroenterology 20220501 2

Encorafenib, a BRAF kinase inhibitor, in combination with binimetinib, a selective MEK inhibitor have known gastrointestinal adverse events; however, adverse colitis events have not been well studied. We report a case series of 4 patients with melanoma who developed inflammatory colitis after BRAF and MEK inhibition with encorafenib and binimetinib, respectively. In the setting of immune checkpoint inhibitor use, BRAF and MEK inhibitors can cause significant inflammatory colitis with endoscopic ...[more]

PMID: 35949237

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Project description:BackgroundImmune-mediated diarrhea and colitis (IMDC) can limit immune checkpoint inhibitors (ICIs) treatment, which is efficacious for advanced malignancies. Steroids and infliximab are commonly used to treat it. These agents induce systemic immunosuppression, with its associated morbidity. We assessed clinical outcomes of vedolizumab as an alternative treatment for IMDC.MethodsWe analyzed a retrospective case series of adults who had IMDC refractory to steroids and/or infliximab and received vedolizumab from 12/2016 through 04/2018.ResultsTwenty-eight patients were included. The median time from ICI therapy to IMDC onset was 10?weeks. Fifteen patients (54%) had grade 2 and 13 (46%) had grade 3 or 4 IMDC. Mucosal ulceration was present in 8 patients (29%), and nonulcerative inflammation was present in 13 (46%). All patients had features of active histologic inflammation; 14 (50%) had features of chronicity, and 10 (36%) had features of microscopic colitis concurrently. The mean duration of steroid therapy was 96?days (standard deviation 74?days). Nine patients received infliximab in addition to steroids and their IMDC was refractory to it. Among these, the duration of steroid use was 131?days compared with 85?days in patients who did not receive infliximab. Likewise, patients who failed infliximab before vedolizumab had a clinical success rate of 67% compared to 95% for patients that did not receive infliximab. The median number of vedolizumab infusions was 3 (interquartile range 1-4). The mean duration of follow-up was 15?months. Twenty-four patients (86%) achieved and sustained clinical remission. Repeat endoscopic evaluation was performed in 17 patients. Endoscopic remission was attained in 7 (54%) of the 13 patients who had abnormal endoscopic findings initially; 5/17 patients (29%) reached histologic remission as well.ConclusionsVedolizumab can be appropriate for the treatment of steroid-refractory IMDC, with favorable outcomes and a good safety profile.

Dataset Information

Severe Inflammatory Colitis Related to Encorafenib and Binimetinib following Immune Checkpoint Inhibitor Therapy.

Publications

Severe Inflammatory Colitis Related to Encorafenib and Binimetinib following Immune Checkpoint Inhibitor Therapy.

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