Evaluation of colitis induced by immune-checkpoint inhibitors therapy in melanoma patients by an overall grading scale.

BACKGROUND: Colitis was the third most common immune-related adverse effect in melanoma patients treated with immune-checkpoint inhibitor (ICI). With the limitation of real-world data in the UK population, this study was conducted in a UK hospital where a fresh colitis guidance was introduced to evaluate the overall grading (OG) to assess colitis severity and guide the treatment. AIMS: This study aimed to investigate colitis severity by Common Terminology Criteria for Adverse Events (CTCAE) grade and overall grade at time of presentation. Colitis treatment and outcome were evaluated to compare the impact of these two categories. METHODS: A single-center, retrospective observational study was performed in melanoma patient developing colitis symptoms. RESULTS: A total of 44 advanced melanoma patient with colitis symptoms were included. Median time to colitis onset was 67 days (range 4-890). Majority of patients developed G1/ G2 of CTCAE scale (70.4%) but moderate or severe overall grade (84.1%). There were 65.9% of patients treated with steroids, and 38.2% with infliximab and 4.5% with vedolizumab. The median time of colitis resolution was 28 days (range 0-282). Both treatment modality and time to resolution were associated with severity of colitis assessed by complete OG(p<0.0001) rather than CTCAE grading (p>0.05). CONCLUSIONS: This study provided a comprehensive description about ICI-induced colitis management in a single center of the UK. The more completed OG was proposed to stratify colitis patient and guide the investigation and treatment decision at presenting time, replacing the old CTCAE grading.

Management of immune-related hepatitis in patients being treated with checkpoint inhibitors for metastatic melanoma, a review and case series.

INTRODUCTION: Immune-related hepatitis is an adverse effect following treatment with immune-checkpoint inhibitors, such as ipilimumab, nivolumab and pembrolizumab. International guidelines advise on the use of corticosteroids as first-line treatment, although guidance on how to treat cases resistant to corticosteroids is limited. We aimed to evaluate the presentation and management of patients with grade 3-4 immune-related hepatitis, following treatment with immune-checkpoint inhibitors for stage 4 or unresectable or stage 3 melanoma, with a particular focus on steroid-refractory cases. METHODS: A retrospective observational review of patients developing immune-related hepatitis whilst undergoing treatment with immune checkpoint inhibitors for advanced melanoma from July 2014 to February 2020 at a tertiary oncology centre. RESULTS: Forty-one patients developed immune-related hepatitis, of which 83% had been treated with the combination of ipilimumab and nivolumab. The median time to onset of IR-hepatitis was 47 days (range: 4-476), and the median time to peak alanine aminotransferase was 71 days (range: 4-478). Four patients had resolution of grade 3 immune-related hepatitis without the introduction of corticosteroids. A total of 37 patients were treated with corticosteroids. A total of 12 required oral treatment only and 13 were successfully managed as outpatients. Six patients had steroid-refractory immune-related hepatitis; and all received tacrolimus, with one also receiving mycophenolate mofetil and infliximab. CONCLUSIONS: This study describes the largest UK series of immune-related hepatitis patients in the literature. We present two important deviations from current guidelines. Firstly, there is some evidence that withholding steroids is possible in grade 3-4 immune-related hepatitis. Secondly, tacrolimus can be used successfully to manage patients resistant to corticosteroids, with the early introduction most beneficial to reduce time on steroids.