Impact of Aging on Rheumatic Immune-related Adverse Events Secondary to Immune Checkpoint Inhibitors: Experience from the Canadian Research Group of Rheumatology in Immuno-Oncology (CanRIO)

Jenny Li¹, Marie Hudson², Carrie Ye³, Janet Roberts⁴, Aurore Fifi-Mah⁵, May Choi⁵, Sabrina Hoa⁶, Thomas Appleton⁷, Janet Pope⁷, Nancy Maltez⁸, Lourdes Gonzalez Arreola⁹, Anthony Obrzut⁹ and Shahin Jamal¹⁰, ¹University of British Columbia, Vancouver, BC, Canada, ²McGill University, Montréal, QC, Canada, ³University of Alberta, Edmonton, AB, Canada, ⁴Dalhousie University, Halifax, NS, Canada, ⁵University of Calgary, Calgary, AB, Canada, ⁶University of Montreal, Brossard, QC, Canada, ⁷University of Western Ontario, London, ON, Canada, ⁸The Ottawa Hospital, Ottawa, ON, Canada, ⁹Arthritis Research Canada, Vancouver, BC, Canada, ¹⁰Vancouver Coastal Health, Vancouver, BC, Canada

Meeting: ACR Convergence 2023

Keywords: Aging, Disease Activity, Drug toxicity, Inflammation, risk factors

Session Information

Date: Monday, November 13, 2023

Title: (1052–1081) Immunological Complications of Medical Therapy Poster

Session Type: Poster Session B

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

Background/Purpose: Immune checkpoint inhibitors (ICI) have revolutionized cancer therapy. Their use is complicated by development of immune-related adverse effects (irAEs), including rheumatic irAEs (Rh-irAE). Aging is known to be associated with an increase in chronic inflammation, likely driven by age-related changes in inflammatory networks and proinflammatory pathways, referred to as “inflammaging”. Older age has been implicated with the development of more frequent and severe irAEs. In this study, we aim to examine whether older patients with Rh-irAEs develop more severe Rh-irAEs or greater number of irAEs compared to younger patients.

Methods: Adults who develop new Rh-irAEs after ICI exposure are prospectively followed at 9 academic sites across Canada as part of the CanRIO prospective cohort. We compared the severity and number of irAE between patients ≥65 years and < 65 years, using logistic regression and Poisson regression, respectively. As part of secondary analysis, we compared the immunosuppression and cancer treatment received in both groups.

Results: 139 Patients with de novo Rh-irAEs recruited between Jan 2020 and March 2023 were included, 58 in the “younger” ( < 65 years) and 81 in the “older” (≥65 years) group (Table 1).There was no significant difference in severity of Rh-irAE (p =0.86) or number of irAEs in each group (p = 0.283) (Table 2). Treatment of irAEs was similar between the two groups, with most patients receiving prednisone monotherapy, conventional synthetic DMARD (csDMARD) monotherapy, or combinations of prednisone/csDMARDs. Biologic DMARDs were infrequently used in both groups. ICI use was similar in both groups. There was a trend towards more severe joint-related Rh-irAEs in the younger group (32% vs 24%, p-value = 0.400), and more severe non-joint related Rh-irAEs (12% vs. 26%, p-value = 0.292) in the older group.

Conclusion: There is growing literature on the role of aging and autoimmunity, but limited data on the relationship between aging and autoimmune reactions, especially after exposure to ICI. In this prospective cohort study, we found similar numbers of overall irAE and severity of Rh-irAE in older and younger patients and similar treatment in both groups. As the role of immunotherapy continues to expand, further investigations in this area can provide insight on whether age-related changes in the immune system influence the development, severity, and clinical course of irAE, which may impact patient counselling and underlying cancer therapy.

ICI = immune checkpoint inhibitor

a. Three people in each of the younger and older group have 2 Rh-irAEs each. b. Eleven people from the younger group and 10 people from the older group have ≥2 non-Rh-irAEs each. IrAE = immune-related adverse event; Rh-irAE = rheumatic immune-related adverse event; Ir = immune-related; CTCAE = Common Terminology Criteria for Adverse Events; ICI = immune checkpoint inhibitor

Disclosures: J. Li: None; M. Hudson: AstraZeneca, 6, Boehringer-Ingelheim, 1, 5, 6, Bristol-Myers Squibb(BMS), 5, Merck, 6, UCB, 5; C. Ye: None; J. Roberts: None; A. Fifi-Mah: Bristol-Myers Squibb(BMS), 5, Celltrion, 1, Frenesius-Kabi, 6, Novartis, 1, Otsuka, 1, Pfizer, 5, Sanofi, 1; M. Choi: AbbVie/Abbott, 2, 6, Amgen, 2, 6, AstraZeneca, 2, 6, Bristol-Myers Squibb(BMS), 2, 6, Celgene, 2, 6, Eli Lilly, 2, 6, GlaxoSmithKlein(GSK), 2, Janssen, 2, 6, Mallinckrodt, 2, Merck/MSD, 2, MitogenDx, 2, Organon, 6, Pfizer, 2, 6, Roche, 2, Werfen, 2; S. Hoa: Boehringer-Ingelheim, 5; T. Appleton: AbbVie/Abbott, 1, 2, 6, AstraZeneca, 1, 1, Celgene, 1, Eli Lilly, 1, Janssen, 1, Novartis, 1, 2, 5, 6, Pfizer, 1, 2, 5, 6, Roche, 1, UCB, 1, 2, 6; J. Pope: AbbVie, 1, 2; N. Maltez: None; L. Gonzalez Arreola: None; A. Obrzut: None; S. Jamal: AbbVie/Abbott, 1, 6, Eli Lilly, 1, GlaxoSmithKlein(GSK), 1, Merck/MSD, 1, 5, Pfizer, 1, 2, 6, UCB, 1, 2, 6.

To cite this abstract in AMA style:

Li J, Hudson M, Ye C, Roberts J, Fifi-Mah A, Choi M, Hoa S, Appleton T, Pope J, Maltez N, Gonzalez Arreola L, Obrzut A, Jamal S. Impact of Aging on Rheumatic Immune-related Adverse Events Secondary to Immune Checkpoint Inhibitors: Experience from the Canadian Research Group of Rheumatology in Immuno-Oncology (CanRIO) [abstract]. Arthritis Rheumatol. 2023; 75 (suppl 9). https://acrabstracts.org/abstract/impact-of-aging-on-rheumatic-immune-related-adverse-events-secondary-to-immune-checkpoint-inhibitors-experience-from-the-canadian-research-group-of-rheumatology-in-immuno-oncology-canrio/. Accessed .

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