Anti-PD-1 therapy in patients with advanced melanoma and preexisting autoimmune disorders or major toxicity with ipilimumab

Alexander M. Menzies*, D. B. Johnson, S. Ramanujam, V. G. Atkinson, A. N. M. Wong, J. J. Park, J. L. McQuade, A. N. Shoushtari, K. K. Tsai, Z. Eroglu, O. Klein, J. C. Hassel, J. A. Sosman, A. Guminski, R. J. Sullivan, A. Ribas, M. S. Carlino, M. A. Davies, S. K. Sandhu, G. V. Long

*Corresponding author for this work

Research output: Contribution to journalArticle

305 Citations (Scopus)

Abstract

Background: 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 immunerelated adverse events (irAEs) with ipilimumab. We sought to explore the safety and efficacy of anti-PD-1 in such patients. Patients and methods: 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. Results: 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. Conclusions: 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.

Original languageEnglish
Pages (from-to)368-376
Number of pages9
JournalAnnals of Oncology
Volume28
Issue number2
DOIs
Publication statusPublished - 2017
Externally publishedYes

Keywords

  • Autoimmune disorder
  • Autoimmunity
  • Cancer
  • Immunotherapy
  • Melanoma
  • PD-1

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