Anti-PD-1 therapy in patients with advanced melanoma and preexisting autoimmune disorders or major toxicity with ipilimumab.
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.
Melanoma Institute Australia and The University of Sydney, Sydney, Australia.|Royal North Shore and Mater Hospitals, Sydney, Australia.
A M
AM
Menzies
Vanderbilt University Medical Center, Nashville, USA.
D B
DB
Johnson
Melanoma Institute Australia and The University of Sydney, Sydney, Australia.
S
S
Ramanujam
Princess Alexandra Hospital, Greenslopes Hospital and University of Queensland, Brisbane, Australia.
V G
VG
Atkinson
Peter MacCallum Cancer Centre, Melbourne, Australia.
A N M
ANM
Wong
Crown Princess Mary Cancer Centre Westmead, Sydney, Australia.
J J
JJ
Park
The University of Texas MD Anderson Cancer Center, Houston, USA.
J L
JL
McQuade
Memorial Sloan Kettering Cancer Center, New York, USA.
A N
AN
Shoushtari
Department of Medical Oncology, University of California San Francisco, San Francisco, USA.
K K
KK
Tsai
Department of Medical Oncology, Moffitt Cancer Centre, Tampa, USA.
Z
Z
Eroglu
Department of Medical Oncology, Olivia Newton-John Cancer Centre & Cancer Research Institute, Austin Health, Melbourne, Australia.
O
O
Klein
Department of Dermatology, Heidelberg University, Heidelberg, Germany.
J C
JC
Hassel
Vanderbilt University Medical Center, Nashville, USA.
J A
JA
Sosman
Melanoma Institute Australia and The University of Sydney, Sydney, Australia.|Royal North Shore and Mater Hospitals, Sydney, Australia.
A
A
Guminski
Massachusetts General Hospital Cancer Center, Boston, USA.
R J
RJ
Sullivan
Division of Hematology-Oncology, University of California Los Angeles, Los Angeles, USA.
A
A
Ribas
Melanoma Institute Australia and The University of Sydney, Sydney, Australia.|Crown Princess Mary Cancer Centre Westmead, Sydney, Australia.
M S
MS
Carlino
The University of Texas MD Anderson Cancer Center, Houston, USA.
M A
MA
Davies
Peter MacCallum Cancer Centre, Melbourne, Australia.
S K
SK
Sandhu
Melanoma Institute Australia and The University of Sydney, Sydney, Australia.|Royal North Shore and Mater Hospitals, Sydney, Australia.
G V
GV
Long
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000627:therapeutic use*; D000074322:Antineoplastic Agents, Immunological / Q000009:adverse effects / Q000627:therapeutic use*; D001327:Autoimmune Diseases / Q000139:chemically induced / Q000276:immunology; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D000074324:Ipilimumab / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D008875:Middle Aged; D000077594:Nivolumab; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors; D012189:Retrospective Studies; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D055815:Young Adult
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000074322:Antineoplastic Agents, Immunological; D000074324:Ipilimumab; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D000077594:Nivolumab; C582435:pembrolizumab
PD-1; autoimmune disorder; autoimmunity; cancer; immunotherapy; melanoma
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