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Original Investigation
February 2016

Ipilimumab Therapy in Patients With Advanced Melanoma and Preexisting Autoimmune Disorders

Author Affiliations
  • 1Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee
  • 2Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts
  • 3Department of Medicine, Dana-Farber Cancer Institute, Boston, Massachusetts
  • 4Department of Medicine, Crown Princess Mary Cancer Centre, Westmead and Blacktown Hospitals, Sydney, New South Wales, Australia
  • 5Department of Medicine, University of Sydney, Sydney, New South Wales, Australia
  • 6Department of Medicine, Roswell Park Cancer Institute, Buffalo, New York
  • 7Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee
  • 8Department of Medicine, Melanoma Institute Australia, Sydney, New South Wales, Australia
  • 9medical student at School of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee
  • 10Department of Medicine, Rutgers Cancer Institute of New Jersey, New Brunswick
  • 11Department of Medicine, Heidelberg University Hospital, Heidelberg, Germany
  • 12Department of Surgery, Rutgers Cancer Institute of New Jersey, New Brunswick
  • 13Department of Medicine, Loyola University Medical Center, Maywood, Illinois
JAMA Oncol. 2016;2(2):234-240. doi:10.1001/jamaoncol.2015.4368

Importance  Ipilimumab and other immune therapies are effective treatment options for patients with advanced melanoma but cause frequent immune-related toxic effects. Autoimmune diseases are common, and the safety and efficacy of ipilimumab therapy in patients with preexisting autoimmune disorders is not known.

Objective  To determine the safety and efficacy of ipilimumab therapy in patients with advanced melanoma with preexisting autoimmune disorders.

Design, Setting, and Participants  Retrospective review of patients with advanced melanoma and preexisting autoimmune disorders who received ipilimumab at 9 academic tertiary referral centers from January 1, 2012, through August 1, 2015. The data analysis was performed on August 24, 2015.

Exposure  Ipilimumab therapy.

Main Outcomes and Measures  Safety, in terms of frequency of autoimmune flares and conventional immune-related adverse events (irAEs), and efficacy, in terms of response rates and overall survival, were evaluated descriptively.

Results  Of the 30 patients who received ipilimumab (17 [57%] male; median [range] age, 59.5 [30-80] y), 6 had rheumatoid arthritis, 5 had psoriasis, 6 had inflammatory bowel disease, 2 had systemic lupus erythematosus, 2 had multiple sclerosis, 2 had autoimmune thyroiditis, and 7 had other conditions. Thirteen patients (43%) were receiving immunosuppressive therapy at the time of initiation of ipilimumab therapy, most commonly low-dose prednisone or hydroxychloroquine. With ipilimumab treatment, 8 patients (27%) experienced exacerbations of their autoimmune condition necessitating systemic treatment; all were managed with corticosteroids. Conventional grade 3 to 5 irAEs occurred in 10 patients (33%) and were reversible with corticosteroids or with infliximab therapy in 2 cases. One patient with baseline psoriasis died of presumed immune-related colitis after a 1-week delay prior to reporting symptoms. Fifteen patients (50%) had neither autoimmune disease flares nor irAEs. Six patients experienced an objective response (20%), including 1 with a durable complete response.

Conclusions and Relevance  To our knowledge, this is the largest series of patients with preexisting autoimmune disease treated with immune checkpoint inhibitors. Ipilimumab was clinically active and was associated with exacerbations of autoimmune disease and conventional ipilimumab-induced irAEs that were readily manageable with standard therapies when started in a timely fashion. Ipilimumab therapy may be considered in this setting with vigilant clinical monitoring.