CHSU Discovery

Abstract:

Introduction and Background: In 2011, there were over 65,000 cases and over 9,000 deaths from melanoma in the United States, alone. Targeted therapy and immunotherapy were landmark steps in melanoma treatment but combined immunotherapy has been a recent breakthrough in treatment that has prolonged progression free and overall survival A recent trial has demonstrated combined therapy with an anti-PD-1 drug and anti-CTLA4 agent, i.e. nivolumab and ipilimumab, respectively, has demonstrated greater sensitivity to therapy than monotherapy alone and up to a 60% response in patients with metastatic melanoma Despite the promising results, severe adverse events have also significantly increased with combined therapy than monotherapy alone. One of the most significant adverse side effects that leads to intolerance and discontinuation is immune-mediated colitis (IMC) and diarrhea. 

Materials and Methods: The goal of our case series was to describe the combined usage of cholestyramine and tincture of opiate in effectively managing immune checkpoint inhibitor-induced colitis that is encountered in treatment of melanoma. A 24-year-old female with metastatic melanoma, with cerebral metastases, treated with Keytruda® (pembrolizumab) presented with significant distress due to incessant diarrhea. The patient and her mother kept a daily count of loose stools as they were concerned with the excessive frequency. The patient initially received solumedrol for the immunotherapy-induced diarrhea yet was still having an average of 14 to 16 loose stools daily. Additionally, the patient had confusion secondary to cerebral edema so we replaced her solumedrol with dexamethasone which had better blood-brain barrier penetration to improve her lucidity while continuing to treat the immune-mediated colitis. The frequency of her stools remained unchanged and we initiated a combination of cholestyramine and tincture of opiate which significantly improved the frequency of her stools to only 3-4 episodes per day down from 14-16 per day. 
Another unique example is the case of a 62-year-old female who had metastatic melanoma treated with Keytruda® followed by resolution of the metastatic lesion. Despite cessation of immunotherapy, the patient had unrelenting and distressing diarrhea a month later and solumedrol was ineffective. After a prolonged trial of corticosteroids, she opted to try our recommendation of treatment with tincture of opiate and cholestyramine. Again, we were successful in reducing her diarrhea from approximately 12 episodes per day down to 5 episodes per day and to the patient, most importantly, we improved her quality of life. 

Results and Conclusion: Based on our illustrated report, we recommend using a multi-modal approach to more effectively control colitis and diarrhea using a tincture of opiate, cholestyramine then corticosteroid therapy.