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Title: Anti-PD-1 therapy in patients with advanced melanoma and preexisting autoimmune disorders or major toxicity with ipilimumab.
Austin Authors: Menzies, A M;Johnson, D B;Ramanujam, S;Atkinson, V G;Wong, A N M;Park, J J;McQuade, J L;Shoushtari, A N;Tsai, K K;Eroglu, Z;Klein, Oliver ;Hassel, J C;Sosman, J A;Guminski, A;Sullivan, R J;Ribas, A;Carlino, M S;Davies, M A;Sandhu, S K;Long, G V
Affiliation: Department of Dermatology, Heidelberg University, Heidelberg, Germany
Department of Medical Oncology, Olivia Newton-John Cancer Wellness and Research Centre, Austin Health, Heidelberg, Victoria, Australia
Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia
Division of Hematology-Oncology, University of California Los Angeles, Los Angeles, USA
Princess Alexandra Hospital, Greenslopes Hospital and University of Queensland, Brisbane, Australia
Peter MacCallum Cancer Centre, Melbourne, Australia
Crown Princess Mary Cancer Centre Westmead, Sydney, Australia
Vanderbilt University Medical Center, Nashville, USA
Massachusetts General Hospital Cancer Center, Boston, USA
Department of Medical Oncology, Moffitt Cancer Centre, Tampa, USA
Department of Medical Oncology, University of California San Francisco, San Francisco, USA
Memorial Sloan Kettering Cancer Center, New York, USA
The University of Texas MD Anderson Cancer Center, Houston, USA
Melanoma Institute Australia and The University of Sydney, Sydney, Australia
Royal North Shore and Mater Hospitals, Sydney, Australia
Issue Date: 1-Feb-2017
Publication information: Annals of oncology : official journal of the European Society for Medical Oncology 2017; 28(2): 368-376
Abstract: Anti-PD-1 antibodies (anti-PD-1) have clinical activity in a number of malignancies. All clinical trials have excluded patients with significant preexisting autoimmune disorders (ADs) and only one has included patients with immune-related adverse events (irAEs) with ipilimumab. We sought to explore the safety and efficacy of anti-PD-1 in such patients. Patients with advanced melanoma and preexisting ADs and/or major immune-related adverse events (irAEs) with ipilimumab (requiring systemic immunosuppression) that were treated with anti-PD-1 between 1 July 2012 and 30 September 2015 were retrospectively identified. One hundred and nineteen patients from 13 academic tertiary referral centers were treated with anti-PD-1. In patients with preexisting AD (N = 52), the response rate was 33%. 20 (38%) patients had a flare of AD requiring immunosuppression, including 7/13 with rheumatoid arthritis, 3/3 with polymyalgia rheumatica, 2/2 with Sjogren's syndrome, 2/2 with immune thrombocytopaenic purpura and 3/8 with psoriasis. No patients with gastrointestinal (N = 6) or neurological disorders (N = 5) flared. Only 2 (4%) patients discontinued treatment due to flare, but 15 (29%) developed other irAEs and 4 (8%) discontinued treatment. In patients with prior ipilimumab irAEs requiring immunosuppression (N = 67) the response rate was 40%. Two (3%) patients had a recurrence of the same ipilimumab irAEs, but 23 (34%) developed new irAEs (14, 21% grade 3-4) and 8 (12%) discontinued treatment. There were no treatment-related deaths. In melanoma patients with preexisting ADs or major irAEs with ipilimumab, anti-PD-1 induced relatively frequent immune toxicities, but these were often mild, easily managed and did not necessitate discontinuation of therapy, and a significant proportion of patients achieved clinical responses. The results support that anti-PD-1 can be administered safely and can achieve clinical benefit in patients with preexisting ADs or prior major irAEs with ipilimumab.
DOI: 10.1093/annonc/mdw443
Journal: Annals of oncology : official journal of the European Society for Medical Oncology
PubMed URL: 27687304
Type: Journal Article
Subjects: PD-1
autoimmune disorder
Appears in Collections:Journal articles

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