Management of immune-related hepatitis in patients being treated with checkpoint inhibitors for metastatic melanoma, a review and case series
Tew, Alice Khoja, Leila Pallan, Lalit Steven, Neil
Tew, Alice
Khoja, Leila
Pallan, Lalit
Steven, Neil
Abstract
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.
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Date
2022-05-23
Type
Article
Subject
Oncology. Pathology., Pharmacology
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Citation
Tew A, Khoja L, Pallan L, Steven N. Management of immune-related hepatitis in patients being treated with checkpoint inhibitors for metastatic melanoma, a review and case series. J Oncol Pharm Pract. 2023 Jul;29(5):1163-1171. doi: 10.1177/10781552221103548. Epub 2022 May 23. PMID: 35607278.
Journal / Source Title
Journal of Oncology Pharmacy Practice
DOI
10.1177/10781552221103548
PMID
35607278
Publisher
SAGE Publications
Publisher’s URL
https://journals.sagepub.com/home/opp