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Abstract Number: 2158

Rheumatic Immune Related Adverse Events Associated with Cancer Immunotherapy: A Nationwide Multi-centre Canadian Cohort from the Canadian Research Group of Rheumatology in Immuno-oncology (CanRIO)

Janet Roberts1, Daniel Ennis 2, Marie Hudson 3, Carrie Ye 4, Alexandra Saltman 5, Sabrina Hoa 6, Janet Pope 7, Megan Himmel 2, Nancy Maltez 8, Aurore Fifi-Mah 9, Annaliese Tisseverasinghe 10, Robert Rottapel 11, Karam Al Jumaily 12, Christina Ly 13, Liliana Cartagena 14 and Shahin Jamal 15, 1Dalhousie University, Halifax, NS, Canada, 2University of Toronto, Toronto, ON, Canada, 3Jewish General Hospital, Lady Davis Institute for Medical Research, and Department of Medicine, McGill University, Montreal, QC, Canada, 4University of Alberta, Edmonton, AB, Canada, 5University of Toronto, Mount Sinai Hospital and Princess Margaret Cancer Centre, Toronto, ON, Canada, 6University of Montreal, Montreal, QC, Canada, 7Western University, London, ON, Canada, 8University of Ottawa, Ottawa, ON, Canada, 9University of Calgary, Calgary, AB, Canada, 10University of Manitoba, Winnipeg, MB, Canada, 11University of Toronto, Toronto, Canada, 12University of Alberta, edmonton, Canada, 13McGill University, Montreal, Canada, 14Arthritis Research Canada, Vancouver, Canada, 15University of British Columbia, Vancouver, BC, Canada

Meeting: 2019 ACR/ARP Annual Meeting

Keywords: adverse events and cohort, Cancer, Cancer treatments, Immunotherapy

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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 (ICI) have revolutionized cancer therapy by harnessing the immune system to fight cancer.  They are associated with the development of autoimmune toxicities, referred to as immune-related adverse events (irAE).  Rheumatic irAE (Rh-irAE), particularly arthralgias and arthritis are common and optimal management remains unknown.   The Canadian Research Group of Rheumatology in Immuno-Oncology (CanRIO) is an emerging network of Canadian rheumatologists with an interest in Rh-irAE secondary to ICI.

Methods: Patients presenting with rheumatic symptoms associated with ICI therapy between 2013 and January 2019 at participating CanRIO sites were identified. Cases were stratified based on the presence or absence of pre-existing autoimmune disease (PAD).  Standardized data were extracted by chart review. The data were pooled and analyzed descriptively.

Results: A total of 118 patients without PAD who developed 140 Rh-irAE were identified, 59% were male with a mean age of 62 years. The most common indications for ICI were melanoma (n=57, 48.3%), lung (n=30, 25.4%), and genitourinary (n=19, 16.1%) with stage 4 disease seen in 79%.  ICI included nivolumab (n=30, 25.6%), pembrolizumab(n=38, 32.5%), ipilimumab (n=1, 0.9%), durvalumab (n=3, 2.6%), atezolizumab (n=4, 3.4%) or combination therapy (n=29, 24.8%). Common Rh-irAE included symmetric polyarthritis (n=45, 32%), arthralgias/myalgias or acute flare of osteoarthritis (n=20, 16.9%), polymyalgia rheumatica-like presentation (n=17, 12%), tenosynovitis/enthesitis (n=17, 12%), sicca (n=11, 9.3%) and myositis (n=9, 7.6%).

The majority of cases experienced at least one other non-rheumatic irAE (O-irAE) (n=63, 53%).  Mean time from first ICI exposure to onset of Rh-irAE was 6.8 months. ICI was either held or discontinued in 65% (n=77). Despite this, (n=81, 68.6%) had favorable tumor response, while (n=14, 12%) had tumor progression.  There were no deaths related to Rh-irAE.

The majority of patients without PAD had either a partial or complete response to either mono- or combination therapy with oral prednisone (n=77; maximum dose 60 mg/d), non-steroidal anti-inflammatories (NSAID; n=52), intra-articular corticosteroids (n=29), hydroxychloroquine (n=26), methotrexate (n=17), or tumor necrosis factor alpha inhibitors (n=9).

Twenty patients with pre-existing autoimmune diseases were identified 70% of whom were in remission prior to starting ICI.  50% (n=10) had flares, 15% (n=3) developed a new Rh-IrAE and 20% (n=4) developed O-irAE.

Conclusion: This is the largest multi-centered cohort of Rh-irAE described to date.  Seronegative inflammatory polyarthritis was the most common Rh-IrAE although a broad range of conditions were identified.  The most common first-line treatment was systemic corticosteroids followed by NSAID and intra-articular steroid injections. Prednisone was effective, however high doses were required.  Disease-modifying antirheumatic drugs (DMARD) and biologic therapy were well tolerated and effective, with hydroxychloroquine being the most commonly used DMARD. Despite moderate to high doses of immunosuppression, the majority of patients had favorable tumor responses.   


Table 1- Demographics and tumor type

Table 1: Demographics and tumor type


Table 2 Rh-irAE and selected investigations

Table 2: Rh-irAE and selected Investigations


Table 3 Effects of ICI on pre-existing autoimmune disease

Table 3: Effects of ICI on pre-existing autoimmune diseases


Disclosure: J. Roberts, None; D. Ennis, None; M. Hudson, None; C. Ye, None; A. Saltman, None; S. Hoa, None; 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; M. Himmel, None; N. Maltez, None; A. Fifi-Mah, Abbvie, 5, BMS, 5, 8, Celgene, 5, Janssen, 5, 8, Pfizer, 8, Roche, 2, 5, Sanofi, 5; A. Tisseverasinghe, None; R. Rottapel, None; K. Al Jumaily, None; C. Ly, None; L. Cartagena, None; S. Jamal, Abbvie, 5, Amgen, 5, BMS, 5, Eli Lilly, 5, Janssen, 5, Merck, 5, Pfizer, 5.

To cite this abstract in AMA style:

Roberts J, Ennis D, Hudson M, Ye C, Saltman A, Hoa S, Pope J, Himmel M, Maltez N, Fifi-Mah A, Tisseverasinghe A, Rottapel R, Al Jumaily K, Ly C, Cartagena L, Jamal S. Rheumatic Immune Related Adverse Events Associated with Cancer Immunotherapy: A Nationwide Multi-centre Canadian Cohort from the Canadian Research Group of Rheumatology in Immuno-oncology (CanRIO) [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/rheumatic-immune-related-adverse-events-associated-with-cancer-immunotherapy-a-nationwide-multi-centre-canadian-cohort-from-the-canadian-research-group-of-rheumatology-in-immuno-oncology-canrio/. Accessed .
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