Lourdes Gonzalez Arreola, Jeremiah Tan, Alexandra Ladouceur, Marie Hudson, Carrie Ye, Janet Roberts, Aurore Fifi-Mah, May Choi, Sabrina Hoa, Tom Appleton, Janet Pope, Nancy Maltez, Shahin Jamal on behalf of the Canadian Research Group of Rheumatology in Immuno-Oncology (CanRIO).

Title: 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)

Background: 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 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 a large French retrospective cohort, patients on immunosuppression at baseline had poorer tumor outcomes (1).

Objectives: To explore the safety and efficacy of ICI in patients with Rh-PAD and to determine if immunosuppression at baseline impacts early tumor outcomes using data from the CanRIO prospective cohort.

Methods: The 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.

Results: Forty 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% Rh-irAE out of which 46.7% were on baseline immunosuppression) and Rh-PAD exacerbations occurred in 25% out of which 60% were on baseline immunosuppression. Of these, 40% were severe with 50% being 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.

Conclusion: Early 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 change in baseline immunosuppression; (3) most patients with Rh-PADs had good tumour response despite baseline immunosuppression when starting ICI.

References:

[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.