Implementing an immunotherapy toxicity (IOTOX) GI service improves outcomes in patients with immune-mediated diarrhea and colitis

Abstract

Purpose: Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy but can lead to GI toxicity, termed immune-mediated diarrhea and colitis (IMDC). Standardization of IMDC management and early GI consultation is imperative to control symptoms and prevent delays in cancer care. Therefore, we implemented an inpatient algorithm and a focused IOTOX GI service to measure outcomes.

Methods: Patients who received ICIs and were hospitalized with severe IMDC were grouped into a pre-interventional cohort in 2017, followed by implementation of the standardized algorithm in 2018, and then a post-interventional cohort of patients in 2019. Clinical data and patient outcomes were compared using univariate and multivariate analysis to determine the morbidity, and overall survival.

Results: Our sample comprised 126 hospitalized patients with IMDC, with 59 patients in the pre-interventional 2017 cohort, and 67 patients in the post-interventional 2019 cohort. We found no significant differences in the clinical severity of IMDC symptoms between the two cohorts (p = 1.03) or median time from ICI exposure to development of IMDC (p = 0.495, respectively). After implementing the standardized algorithm, we observed higher rates of GI consultation (p < 0.001) in the post-treatment group. Patients in the post-treatment cohort showed decreased time to clinical remission (4 vs 10 days, p = 0.046), higher rate of GI follow-up after hospital discharge (p = 0.038), fewer hospital re-admissions (p = 0.002), and significantly fewer recurrences of IMDC symptoms (p = 0.002). Overall survival was significantly higher for at least 2 years in patients who followed with GI post-discharge compared to those without follow-up (p = 0.003).

Conclusion: Prompt GI consultation and monitoring of IMDC using a regimented approach can provide efficacious management, decrease time to clinical remission of symptoms, decrease re-admissions to the hospital, and improve overall patient outcomes.

Keywords: Immune checkpoint inhibitor; Immune-mediated diarrhea and colitis; Quality improvement; Selective immunosuppressive therapy.

Fig. 1

Impact of MDACC institutional colitis algorithm in management and outcomes between the pre-interventional cohort (2017) and post-interventional cohort (2019). A Differences in management of patients with IMDC before and after implementation of the MDACC algorithm show increase in total percentage of GI consults, endoscopy performed, use of SIT, and GI follow-up outpatient; B Outcomes in colitis after utilizing the standardized algorithm show significant decrease in colitis related re-admission, colitis recurrence, and improvement in colitis remission between the pre-treatment and post-treatment groups

Fig. 2

A Kaplan–Meier survival comparison between patients with and without GI follow-up (IMDC diagnosis was the starting point for this calculation). This figure shows a significant increase in overall survival probability in patients who had GI follow-up after IMDC diagnosis up to 4 years from initial diagnosis. The greatest difference in survival probability occurred up to 2 years from IMDC diagnosis. B Kaplan–Meier survival curve analyzing cumulative survival of the total combined interventions by the IOTOX GI service including GI consultation, endoscopy for initial IMDC, and GI follow-up within 15 days of discharge. A COX regression analysis showed HR 0.620 [95% CI 0.374–1.018] p = 0.059