Tu1876 – Fecal Microbiota Transplantation for Immune Checkpoint Inhibitor Induced-Colitis Resistant to Immunosuppressive Therapy

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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Outcomes after early initiation of nonsteroidal immunosuppressive therapy in patients with immune checkpoint inhibitor-induced colitis.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.2571 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 2571-2571

Author(s):

Yinghong Wang ◽

Hamzah Abu-Sbeih ◽

Faisal Ali ◽

Mehmet Altan ◽

Ramona Dadu ◽

...

Keyword(s):

Immunosuppressive Therapy ◽

Clinical Outcomes ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitor ◽

Treatment Guidelines ◽

Checkpoint Inhibitor ◽

Fecal Calprotectin ◽

Current Treatment ◽

Duration Of Symptoms ◽

First Line Therapy

2571 Background: Current treatment guidelines for immune-mediated colitis (IMC) recommend 4 to 6 weeks of steroids as first-line therapy, followed by nonsteroidal immunosuppressive therapy (NSIST) (infliximab or vedolizumab) in patients who do not respond to steroids. We assessed the effect of early NSIST introduction and number of NSIST infusions on clinical outcomes. Methods: We performed a retrospective review of patients with IMC who received NSIST between January and December 2018. Logistic regression analyses were used to assess associations between clinical features and outcomes of IMC (Table). Results: Of the 1,459 patients who received immune checkpoint inhibitor, 179 developed IMC of any grade; 84 of them received NSIST. Of the 84 patients who received NSIST, 79% were males with mean age of 60. Compared with patients who received NSIST >10 days after IMC onset, patients who received early NSIST (≤10 days) required fewer hospitalizations ( P=0.03), experienced steroid taper failure less frequently ( P=0.03), had fewer steroid tapering attempts ( P<0.01), had a shorter course of steroid treatment ( P=0.09), and had a shorter duration of symptoms ( P<0.01). Risk factors of IMC recurrence after weaning off steroids included: 1) needing multiple hospitalizations ( P<0.01), 2) experiencing steroid taper failure after NSIST ( P=0.02), 3) receiving infliximab rather than vedolizumab ( P=0.02), 4) receiving fewer than three infusions of NSIST ( P=0.02), 5) having higher fecal calprotectin levels after NSIST ( P=0.01), and 6) receiving a longer course of steroids ( P=0.02), hospitalization ( P<0.01) and IMC symptoms ( P<0.01). Unsuccessful weaning from steroids after NSIST was associated with high IMC grades ( P<0.01); multiple hospitalizations ( P<0.01); steroid-resistant IMC ( P<0.01); long interval from IMC to NSIST initiation ( P=0.01); and long duration of steroids ( P<0.01), IMC symptoms ( P<0.01), and hospitalization ( P<0.01). Conclusions: NSIST should be introduced early in the disease course of IMC instead of waiting until failure of steroid therapy or steroid taper. Patients who received three or more infusions of NSIST had more favorable clinical outcomes.

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