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. 2017 Feb 1;28(2):368-376.
doi: 10.1093/annonc/mdw443.

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

A M Menzies  1   2 , D B Johnson  3 , S Ramanujam  1 , V G Atkinson  4 , A N M Wong  5 , J J Park  6 , J L McQuade  7 , A N Shoushtari  8 , K K Tsai  9 , Z Eroglu  10 , O Klein  11 , J C Hassel  12 , J A Sosman  3 , A Guminski  1   2 , R J Sullivan  13 , A Ribas  14 , M S Carlino  1   6 , M A Davies  7 , S K Sandhu  5 , G V Long  1   2
Affiliations

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

A M Menzies et al. Ann Oncol. .

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 immune-related 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.

Keywords: PD-1; autoimmune disorder; autoimmunity; cancer; immunotherapy; melanoma.

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Figures

Figure 1
Figure 1
Progression-free survival with anti-PD-1 antibodies (A) patients with autoimmune disease, (B) patients with prior ipilimumab toxicity.
See this image and copyright information in PMC

Comment in

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