Preexisting Autoimmune Disease and Rheumatic Immune-Related Adverse Events Associated with Cancer Immunotherapy: A Case Series from the Canadian Research Group of Rheumatology in Immuno-Oncology (CanRIO)

Linda Laaouad¹, Janet Roberts ², Daniel Ennis ³, Carrie Ye ⁴, Karam Al Jumaily ⁵, Marie Hudson ⁶, Shahin Jamal ⁷, Janet Pope ⁸, Tatiana Nevskaya ⁹, Alexandra Saltman ¹⁰, Megan Himmel ¹¹, Aurore Fifi-Mah ¹², Annaliese Tisseverasinghe ¹³, Nancy Maltez ¹⁴, Ines Colmegna ¹⁵ and Sabrina Hoa ¹⁶, ¹University of Montreal, Montreal, Canada, ²Dalhousie University, Halifax, Canada, ³University of Toronto, Toronto, ON, Canada, ⁴University of Alberta, Edmonton, AB, Canada, ⁵University of Alberta, Edmonton, Canada, ⁶Jewish General Hospital, Lady Davis Institute for Medical Research, and Department of Medicine, McGill University, Montreal, QC, Canada, ⁷University of British Columbia, Vancouver, BC, Canada, ⁸Western University, London, ON, Canada, ⁹University of Western Ontario, London, ON, Canada, ¹⁰University of Toronto, Mount Sinai Hospital and Princess Margaret Cancer Centre, Toronto, ON, Canada, ¹¹University of Toronto, Toronto, Canada, ¹²University of Calgary, Calgary, AB, Canada, ¹³University of Manitoba, Winnipeg, MB, Canada, ¹⁴University of Ottawa, Ottawa, ON, Canada, ¹⁵McGill University Health Center, Montreal, QC, Canada, ¹⁶University of Montreal, Montreal, QC, Canada

Meeting: 2019 ACR/ARP Annual Meeting

Keywords: Immunotherapy, Oncology and adverse events, Rheumatic disease

Session Information

Date: Tuesday, November 12, 2019

Title: Miscellanous Rheumatic & Inflammatory Disease Poster III: Autoimmune Conditions and Therapies

Session Type: Poster Session (Tuesday)

Session Time: 9:00AM-11:00AM

Background/Purpose: Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy by harnessing the immune system to fight cancer, but are associated with significant immune-related adverse events (irAEs). Limited data is available on the safety of ICIs in patients with preexisting autoimmune diseases and on concomitant use of immunosuppressive drugs. CanRIO is a network of Canadian rheumatologists with experience in the management of rheumatic irAEs secondary to ICIs. In this case series, we describe the clinical course of patients with preexisting autoimmune diseases who were treated with ICIs at 7 CanRIO sites.

Methods: Patients referred for rheumatological evaluation in the context of immunotherapy between 2013 and March 2019 at participating CanRIO sites with preexisting autoimmune disease were identified. Standardized data were extracted by retrospective chart review. Descriptive statistics were used to summarize the data.

Results: A total of 25 patients with preexisting autoimmune disease who received ICI treatment were identified. Their age was 62.9 ± 11.9 (mean ± SD), 13 (52%) were male, and 23 (92%) were White. Mean (SD) follow-up was 13.1 (9.2) months. The most common indications for ICI were advanced lung cancer (n=13, 52%) and melanoma (n=9, 36%); 96% had stage 4 disease. Most patients received ICI monotherapy (Pembrolizumab: n=17, 68%; Nivolumab: n=6, 24%).

Preexisting autoimmune diseases included rheumatoid arthritis (RA, n=8), psoriasis (n=4), psoriatic arthritis (n=3), axial spondyloarthropathy (SpA, n=3), systemic lupus erythematosus (SLE, n=2), dermatomyositis (n=1), polymyalgia rheumatica (PMR, n=1) and other non-rheumatic diseases (n=3).

Of 8 patients with RA, 71% (5/7) were seropositive (RF ±anti-CCP) and 43% (3/7) had erosive disease. 50% (4/8) were in remission at time of ICI initiation, 29% (2/7) had their DMARDs stopped, 29% (2/7) continued their DMARD(s) and 43% (3/7) had new DMARD(s) started prophylactically. Overall, 50% (4/8) experienced grade ≤ 2 flares of their polyarthritis, 13% (1/8) developed PMR de novoand 38% (3/8) did not have any rheumatic irAE. Of those who developed rheumatic irAEs, 80% (4/5) received Nivolumab, 80% (4/5) had seropositive disease, 63% (5/8) were on DMARDs at time of ICI initiation and 80% (4/5) events occurred after a single dose of ICI.

Of 4 patients with psoriasis but without arthritis, 3 (75%) experienced a flare (both mild and major) of their skin disease and 3 (75%) developed de novo arthritis (grade 2-3) within the first 4 months of ICI treatment. Of 3 patients with axial SpA, two experienced new peripheral arthritis (grade 2) after receiving ICI.

Inflammatory arthritis responded to oral corticosteroids (up to 50 mg, tapered over 4-9 months) and/or addition of DMARDs (methotrexate, hydroxychloroquine and/or sulfasalazine), and required ICI discontinuation in 27% (3/11) of patients. Two patients with SLE remained in remission (on hydroxychloroquine).

Conclusion: This is the largest multicentered study of patients with rheumatic autoimmune diseases exposed to immunotherapy. Arthritis flares in patients with RA exposed to ICI are frequent despite DMARD background therapy. New onset of peripheral arthritis is frequent in SpA and psoriatic patients.

Disclosure: L. Laaouad, None; J. Roberts, None; D. Ennis, None; C. Ye, None; K. Al Jumaily, None; M. Hudson, None; S. Jamal, Abbvie, 5, Amgen, 5, BMS, 5, Eli Lilly, 5, Janssen, 5, Merck, 5, Pfizer, 5; J. Pope, AbbVie, 5, Abbvie, 5, Actelion, 5, Actellion, 5, Amgen, 2, 5, AstraZeneca, 2, Astra-Zeneca, 2, Bayer, 2, 5, BMS, 2, 5, Eicos Sciences, 5, Eli Lilly & Company, 5, Eli Lilly and Company, 5, EMERALD, 5, Emerald, 5, Genzyme, 5, Janssen, 5, Lilly, 5, Merck, 2, 5, Novartis, 5, Pfizer, 2, 5, Roche, 2, 5, Sandoz, 5, Sanofi, 5, Seattle Genetics, 2, UCB, 2, 5, 8; T. Nevskaya, None; A. Saltman, None; M. Himmel, None; A. Fifi-Mah, Abbvie, 5, BMS, 5, 8, Celgene, 5, Janssen, 5, 8, Pfizer, 8, Roche, 2, 5, Sanofi, 5; A. Tisseverasinghe, None; N. Maltez, None; I. Colmegna, None; S. Hoa, None.

To cite this abstract in AMA style:

Laaouad L, Roberts J, Ennis D, Ye C, Al Jumaily K, Hudson M, Jamal S, Pope J, Nevskaya T, Saltman A, Himmel M, Fifi-Mah A, Tisseverasinghe A, Maltez N, Colmegna I, Hoa S. Preexisting Autoimmune Disease and Rheumatic Immune-Related Adverse Events Associated with Cancer Immunotherapy: A Case Series from the Canadian Research Group of Rheumatology in Immuno-Oncology (CanRIO) [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/preexisting-autoimmune-disease-and-rheumatic-immune-related-adverse-events-associated-with-cancer-immunotherapy-a-case-series-from-the-canadian-research-group-of-rheumatology-in-immuno-oncology-canr/. Accessed .

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