Highlights
- •Immune-related hepatitis (ir-hepatitis) is mostly a low-grade toxicity.
- •Severity of ir-hepatitis can be underestimated if only one liver enzyme is measured.
- •A significant risk of ir-hepatitis relapse is seen during steroid tapering.
- •Infections treated with antibiotic treatment could be a potential risk factor for ir-hepatitis.
- •High cumulative steroid dose might have a negative impact on response to checkpoint inhibitors.
Abstract
Introduction
Immune-related hepatitis (ir-hepatitis) is a common side-effect of checkpoint inhibitors
(CPIs). Here, we characterise ir-hepatitis in a large cohort of patients with metastatic
melanoma (MM) treated with CPIs and describe potential risk factors and efficacy of
medical management.
Methods
The retrospective study included a large cohort of patients with MM treated with CPIs
between 2010 and 2019. Patients were retrieved from the national Danish Metastatic
Melanoma Database.
Results
Five hundred twenty one patients were included. Ir-hepatitis was found in 6.8% of
patients. Combination therapy was associated with a significantly greater risk than
monotherapy. Of all patients, 34.9% with hepatitis had a different hepatitis grading,
when based on either alanine transaminase (ALT) or aspartate transaminase (AST) levels.
Of all patients, 72.1% with hepatitis received steroid treatment, and two patients
received additional second-line immunosuppressants. Of all patients, 35.5% experienced
hepatitis relapse during steroid tapering. Of all patients, 18.6% and 25% of patients
with grade ≥2 and ≥ III3, respectively, developed hepatitis within 7 days after finishing
an antibiotic treatment for infection. Patients (62.5%) who received a cumulative
dose of >4000 mg steroid experienced cancer progression, compared with 22.7% of patients
treated with <4000 mg.
Conclusion
Several observations of clinical importance were made. Infection and antibiotic treatment
during CPIs could be a possible risk factor for developing ir-hepatitis. Severity
of ir-hepatitis is potentially underestimated in a significant number of patients,
if only one liver enzyme is measured. The role of second-line immunosuppressants needs
to be further investigated because of the high risk of hepatitis relapse during steroid
tapering and the potential negative impact of cumulative steroid dose on response
to CPIs.
Keywords
Abbreviations:
BOR (best overall response), CR (complete remission), PR (partial remission), PD (progression of the disease), SD (stable disease)To read this article in full you will need to make a payment
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Article info
Publication history
Published online: March 28, 2020
Accepted:
February 13,
2020
Received in revised form:
February 1,
2020
Received:
October 27,
2019
Identification
Copyright
© 2020 Elsevier Ltd. All rights reserved.
