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A multicenter characterization of hepatitis associated with immune checkpoint inhibitors

  • Patrinely, J. Randall Jr.1
  • McGuigan, Ben2
  • Chandra, Sunandana3
  • Fenton, Sarah E.3
  • Chowdhary, Akansha3
  • Kennedy, Lucy B.4
  • Mooradian, Meghan J.5
  • Palmeri, Marisa6
  • Portal, Daniella6
  • Horst, Sara N.7
  • Scoville, Elizabeth A.7
  • Long, Georgina V.2
  • Shi, Chanjuan4
  • Mehnert, Janice M.6
  • Sullivan, Ryan J.5
  • Salama, April K.4
  • Sosman, Jeffrey A.3
  • Menzies, Alexander M.2, 8
  • Johnson, Douglas B.7
  • 1 School of Medicine, Vanderbilt University, USA
  • 2 Melanoma Institute Australia, the University of Sydney, Australia , (Australia)
  • 3 Northwestern Feinberg School of Medicine, USA
  • 4 Duke University Medical Center, USA
  • 5 Massachusetts General Hospital, USA
  • 6 Rutgers Cancer Institute of New Jersey, Rutgers University, USA
  • 7 Vanderbilt University Medical Center, USA
  • 8 Royal North Shore and Mater Hospitals, the University of Sydney, Australia , (Australia)
Published Article
Landes Bioscience
Publication Date
Feb 08, 2021
DOI: 10.1080/2162402X.2021.1875639
PMID: 33628621
PMCID: PMC7889227
PubMed Central


Immune checkpoint inhibitors (ICI) predispose patients to immune-related adverse events (irAEs). Although hepatitis is a potentially lethal toxicity, the timing and outcomes have not been well described. In this retrospective study, patients from six international institutions were included if they were treated with ICIs and developed immune-related hepatitis. Patient and tumor characteristics, and hepatitis management and outcomes were evaluated. Of the 164 patients included, most were male (53.7%) with a median age of 63.0 years. Most patients had melanoma (83.5%) and stage IV disease (86.0%). Median follow-up was 585 days; median OS and PFS were not reached. The initial grade of hepatitis was most often grade 2 (30.5%) or 3 (45.7%) with a median time to onset of 61 days. Patients were most commonly asymptomatic (46.2%), but flu-like symptoms, including fatigue/anorexia (17.1%), nausea/emesis (14.0%), abdominal/back pain (11.6%), and arthralgias/myalgias (8.5%) occurred. Most patients received glucocorticoids (92.1%); the median time to improvement by one grade was 13.0 days, and the median time to complete resolution was 52.0 days. Second-line immunosuppression was required in 37 patients (22.6%), and steroid-dose re-escalation in 45 patients (27.4%). Five patients (3%) died of ICI-hepatitis or complications of hepatitis treatment. Ninety-one patients (58.6%) did not resume ICI; of 66 patients (40 grade 1/2, 26 grade 3/4) that were rechallenged, only 25.8% (n = 17) had recurrence. In this multi-institutional cohort, immune-related hepatitis was associated with excellent outcomes but frequently required therapy discontinuation, high-dose steroids, and second-line immunosuppression. Rechallenge was associated with a modest rate of hepatitis recurrence.

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