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Ann Oncol. 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.

Author information

1
Melanoma Institute Australia and The University of Sydney, Sydney, Australia.
2
Royal North Shore and Mater Hospitals, Sydney, Australia.
3
Vanderbilt University Medical Center, Nashville, USA.
4
Princess Alexandra Hospital, Greenslopes Hospital and University of Queensland, Brisbane, Australia.
5
Peter MacCallum Cancer Centre, Melbourne, Australia.
6
Crown Princess Mary Cancer Centre Westmead, Sydney, Australia.
7
The University of Texas MD Anderson Cancer Center, Houston, USA.
8
Memorial Sloan Kettering Cancer Center, New York, USA.
9
Department of Medical Oncology, University of California San Francisco, San Francisco, USA.
10
Department of Medical Oncology, Moffitt Cancer Centre, Tampa, USA.
11
Department of Medical Oncology, Olivia Newton-John Cancer Centre & Cancer Research Institute, Austin Health, Melbourne, Australia.
12
Department of Dermatology, Heidelberg University, Heidelberg, Germany.
13
Massachusetts General Hospital Cancer Center, Boston, USA.
14
Division of Hematology-Oncology, University of California Los Angeles, Los Angeles, USA.

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

PMID:
27687304
DOI:
10.1093/annonc/mdw443
[Indexed for MEDLINE]

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