Ab1768-Hpr 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

BackgroundImmune 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 disease (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 addition, little is known about optimal use of concurrent immunosuppression and its impact on PAD flares and development of de novo irAE. There is some data that patients on immunosuppression at baseline are at risk for poorer tumor outcomes [1].ObjectivesTo explore the safety and efficacy of ICI in patients with Rh-PAD and to determine if immunosuppression at baseline impacts risk of PAD flare, de-novo irAE and early tumor outcomes using data from the CanRIO prospective cohort.MethodsThe CanRIO cohort includes adult patients with Rh-PAD treated with immune checkpoint inhibitors (ICI, including CTLA-4, PD-1 or PDL-1 inhibitors), recruited across 9 Canadian academic sites and followed prospectively at regular intervals as per a standardized study protocol. In this study, we evaluated patients with Rh-PAD who received at least one dose of ICI.ResultsForty patients with Rh-PADs were recruited into the CanRIO prospective cohort between Jan 2020 and Nov 2022, including 14 (35%) with rheumatoid arthritis, 11 (27.5%) psoriatic arthritis, 7 (17.5%) polymyalgia rheumatica, 5 (12.5%) ankylosing spondylitis and 7 (17.5%) other. The most frequently observed cancers were melanoma 14 (35%) and lung cancer 10 (25%), with stage 3 and stage 4 disease each making up 37.5% of all cases. 25 patients (62.5%) were on baseline immunosuppression prior to ICI start. Anti-PD-1 therapy was most common (45%), followed by combination ICI therapy (22.5%), with a median exposure of 2 months (IQR: 0.5-3.0). Over a median (IQR) follow-up of 3.0 (1.0–6.0) months, 55% experienced a de-novo irAE (68.2% with rh-irAE; of which 46.7% were on baseline immunosuppression), 25% had Rh-PAD flare, of which 60% were on baseline immunosuppression. Of these, 40% were severe (of which 50% on baseline immunosuppression); 70% required corticosteroid treatment; and 40% required a change in immunosuppression. ICI was continued in 50%, transiently held or delayed in 40% and stopped in only 10%. Of the 9 patients on baseline immunosuppression who had been re-staged, 8 had a favorable tumor response (i.e., stabilization, partial or complete response) and only 1 had disease progression.ConclusionEarly data from patients with Rh-PAD in the CanRIO multi-center prospective cohort suggests that (1) ICI can be effective for cancer treatment in patients with Rh-PAD and should be offered as indicated; (2) flares of Rh-PAD are common but can be managed with corticosteroids or escalation of immunosuppression; (3) baseline immunosuppression did not significantly change rate of de-novo irAE or rate/severity of PAD flare (3) most patients with Rh-PADs had good tumour response despite baseline immunosuppression.Reference[1]Tison A, Quéré G, Misery L, Funck-Brentano E, Danlos FX, Routier E, 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.AcknowledgementsWe would like to thank Bristol-Myers Squibb, Merck, and CIORA (Canadian Initiative for Outcomes in Rheumatology cAre) for supporting this study. This content is solely the responsibility of the authors and does not necessarily represent the official views of the sponsors listed here. This research was conducted as part of the Canadian Research Group of Rheumatology in Immuno-Oncology (CanRIO).Disclosure of InterestsLourdes Gonzalez Arreola: None declared, Jeremiah Tan: None declared, Alexandra Ladouceur: None declared, Marie Hudson Consultant of: Consulting fees: Boehringer Ingelheim, Grant/research support from: Unrestricted research grants: Bristol-Myers Squibb, Boehringer Ingelheim; Clinical studies: Astra-Zeneca, Carrie Ye: None declared, Janet Roberts: None declared, Aurore Fifi-Mah: None declared, May Choi: None declared, Sabrina Hoa: None declared, C. Thomas Appleton: None declared, Janet Pope: None declared, Nancy Maltez: None declared, Shahin Jamal: None declared.