Impact of Immunosuppression on the Safety and Efficacy of Immune Checkpoint Inhibitors in Patients with Rheumatic Autoimmune Disease: Experience from the Canadian Research Group of Rheumatology in Immuno-Oncology (CanRIO)

Lourdes Gonzalez Arreola¹, Carrie Ye², Marie Hudson³, Janet Roberts⁴, Janet Pope⁵, Thomas Appleton⁵, Sabrina Hoa⁶, Aurore Fifi-Mah⁷, Nancy Maltez⁸, Alexandra Saltman⁹, Megan Himmel⁹, Ines Colmegna¹⁰, Alexandra Ladouceur¹¹, Anthony Obrzut¹, Jeremiah Tan¹², David Moon², Tatiana Nevskaya⁵, Emma Schmidt¹³, Lindsay Cho⁴, Nader Toban¹⁴ and Shahin Jamal¹⁵, ¹Arthritis Research Canada, Vancouver, BC, Canada, ²University of Alberta, Edmonton, AB, Canada, ³McGill University, Montréal, QC, Canada, ⁴Dalhousie University, Halifax, NS, Canada, ⁵University of Western Ontario, London, ON, Canada, ⁶University of Montreal, Brossard, QC, Canada, ⁷University of Calgary, Calgary, AB, Canada, ⁸The Ottawa Hospital, Ottawa, ON, Canada, ⁹University of Toronto, Toronto, ON, Canada, ¹⁰The Research Institute of the McGill University Health Centre, Montréal, QC, Canada, ¹¹Department of Rheumatology of McGill University and CHU-Bordeaux, Montréal, QC, Canada, ¹²Arthritis Research Canada, Vancouver, Canada, Vancouver, BC, Canada, ¹³University of British Columbia, Vancouver, BC, Canada, ¹⁴Centre Hospitalier de l'Université de Montréal, Dollard-des-Ormeaux, QC, Canada, ¹⁵Vancouver Coastal Health, Vancouver, BC, Canada

Meeting: ACR Convergence 2023

Keywords: autoimmune diseases, Cohort Study, Disease Activity

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 changed the landscape of treatment for many cancers. However, most cancer clinical trials for ICI excluded patients with pre-existing autoimmune diseases (PAD). Efficacy and safety data on the use of ICI in patients with rheumatic PAD (Rh-PAD) is limited to retrospective case series and reports, and many do not differentiate between Rh-PAD and non-rheumatic PAD. In one study of a large French retrospective cohort, patients on immunosuppression (IS) at baseline had poorer tumor outcomes (1).

Objectives: To explore the impact of baseline IS on the safety and efficacy of ICI in patients with Rh-PAD using data from the CanRIO retrospective and prospective cohorts.

Methods: We evaluated patients with Rh-PAD treated with at least one dose of ICI, including CTLA-4, PD-1, or PDL-1 inhibitors. 45 patients were recruited prospectively between Jan 2020 and Apr 2023 across 9 Canadian academic sites and followed at regular intervals as per a standardized study protocol. 57 patients were retrospectively recruited using data extracted from patients referred to rheumatology specialists between Jan 2013 and Jun 2022 across 10 Canadian sites. We used logistic regression to compare the occurrence and severity of flares and de-novo immune-related adverse events (irAE), as well as tumor response, between patients on baseline IS and not on baseline IS.

Results: One hundred and two patients with Rh-PADs were followed for a median of 32 months; 50 were on baseline IS prior to ICI start, and 52 were not. The most common Rh-PADs were rheumatoid arthritis and psoriasis/psoriatic arthritis (Table 1).

Cancer type, cancer stage, ICI type, and ICI exposure time were similar in both groups (Table 1). The flare rate of patients on baseline IS was 58%, compared to only 38% in the group without baseline IS (adjusted OR=2.1; 95% CI = 0.9-5.0; p=0.09). There were no statistically significant differences in the risk of a severe flare (CTCAE grade ≥3) (p = 0.3), development of a de-novo Rh-irAE (p = 0.4) or a severe de-novo Rh-irAE (p = 0.4) (Tables 1 & 2). Tumor follow-up data was available for 38 of the 50 patients on baseline IS and 37 of the 52 patients without baseline IS. The rate of tumor progression was 42% (16 of 38) in the IS group and 27% (10 of 37) in the no IS group (HR=1.4; 95% CI = 0.6-3.1; p=0.437) but there was no difference in progression free survival between groups.

Conclusion: Early data from patients with Rh-PAD in the multicenter prospective and retrospective CanRIO cohorts suggest that 1) ICI can be effective for cancer treatment in patients with Rh-PAD, and should be offered as indicated; 2) Baseline IS does not seem to protect from flares of Rh-PAD; 3) Baseline IS does not seem to change the risk of developing de-novo irAE, nor the severity of flares/de-novo irAEs; 4) There was a non-significant trend towards baseline IS increasing the hazard of tumor progression but no difference in progression free survival between groups.

[1] Tison A, et al. Safety and efficacy of immune checkpoint inhibitors in patients with cancer and preexisting autoimmune disease: A nationwide, Multicenter Cohort Study. Arthritis & Rheumatology. 2019;71(12):2100–11.

Table 1. Summary of demographic, pre-existing rheumatic autoimmune disease, cancer and outcomes data
a 3 patients who were on baseline IS had more than one Rh-PAD; 1 patient who was not on baseline IS had more than one Rh-PAD
b Missing data for 3 patients in the baseline IS group and 1 patient in the no baseline IS group
c 13 patients on baseline IS experienced a flare of their Rh-PAD and a de-novo irAE; 3 patients not on baseline IS experienced a flare of Rh.PAD and de-novo irAEs
d 5 patients on baseline IS experienced both de-novo Rh-irAE and other irAEs; 12 patients not on baseline IS experienced de-novo Rh-irAE and other irAEs
e Including skin, endocrinological (other than thyroid), heart and eyes
f Missing tumor response information for 7 patients on baseline IS and 5 in no baseline IS

Table 2. Flare and de-novo irAEs rates and flare and de-novo irAEs severity according to baseline immunosuppression
a Adjusted for Rheumatic Pre-existing autoimmune disease
(*) Indicates significance at p  0.05. OR calculated using logistic regression

Disclosures: L. Gonzalez Arreola: None; C. Ye: None; M. Hudson: AstraZeneca, 6, Boehringer-Ingelheim, 1, 5, 6, Bristol-Myers Squibb(BMS), 5, Merck, 6, UCB, 5; J. Roberts: None; J. Pope: AbbVie, 1, 2; 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; S. Hoa: Boehringer-Ingelheim, 5; A. Fifi-Mah: Bristol-Myers Squibb(BMS), 5, Celltrion, 1, Frenesius-Kabi, 6, Novartis, 1, Otsuka, 1, Pfizer, 5, Sanofi, 1; N. Maltez: None; A. Saltman: None; M. Himmel: None; I. Colmegna: None; A. Ladouceur: None; A. Obrzut: None; J. Tan: None; D. Moon: None; T. Nevskaya: None; E. Schmidt: None; L. Cho: None; N. Toban: 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:

Gonzalez Arreola L, Ye C, Hudson M, Roberts J, Pope J, Appleton T, Hoa S, Fifi-Mah A, Maltez N, Saltman A, Himmel M, Colmegna I, Ladouceur A, Obrzut A, Tan J, Moon D, Nevskaya T, Schmidt E, Cho L, Toban N, Jamal S. Impact of Immunosuppression on the Safety and Efficacy of Immune Checkpoint Inhibitors in Patients with Rheumatic Autoimmune Disease: 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-immunosuppression-on-the-safety-and-efficacy-of-immune-checkpoint-inhibitors-in-patients-with-rheumatic-autoimmune-disease-experience-from-the-canadian-research-group-of-rheumatology-in-imm/. Accessed .

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