Background Immune Checkpoint Inhibitors (ICI) have altered the landscape of cancer therapy. However, toxicities are common and up to 80% of patients will develop immune-related adverse events (irAE), including rheumatic irAEs (Rh-irAE), which can often limit their cancer treatment. Our knowledge of clinical manifestations and optimal management of patients with Rh-irAE continues to evolve as these agents are being used to treat a wider variety of cancers. Currently available data is limited to retrospective case series and case reports. There is also scarce data on the use of ICI in patients with pre-existing autoimmune disease (PAD) as these patients are often excluded from clinical trials.
Objectives To describe the clinical presentation, management and early outcomes of patients exposed to ICI with Rh-irAE or PAD recruited and followed prospectively from multiple sites across Canada.
Methods Adult patients with Rh-irAE from cancer immunotherapy (CTLA-4, PD-1 or PDL-1 inhibitors) or those with PAD exposed to cancer immunotherapy are prospectively recruited across 9 academic sites in Canada. Standardized clinical and biologic data are also collected. We describe clinical characteristics and management of patients recruited between January 2020 and October 2021, stratified based on the presence or absence of PAD.
Results 103 patients were recruited from 9 sites. From those, 85 had Rh-irAE, 47 had pre-existing musculoskeletal and rheumatic diseases, and 20 had other PAD. The most frequent Rh-irAE were joint manifestations (n = 73). Other Rh-irAE included muscle symptoms (n = 7), connective tissue disease (n = 6), vasculitis (n=2) and sarcoid (n = 3). Prednisone was the most common treatment (n = 53). Intraarticular corticosteroids were used in 7 patients. Eleven patients required conventional synthetic disease-modifying anti-rheumatic drugs (DMARD) and only one required biologic DMARD to control the Rh-irAE. Anti-PD-1 therapies were the most used ICI (56.3%), followed by combination therapy (35.9%). Response to index immunotherapy at 6 months was available for 21 patients. Most patients had partial response (57.1%) and only 4 patients had tumor progression (19.1%). The ICI was permanently discontinued due to an irAE in 21 patients (38.1% with PAD and 61.9% without PAD). There were no deaths related to Rh-irAE.
Conclusion The initial sample of the CanRIO prospective national cohort suggests that demographic characteristics and tumor representation in people with PAD and without PAD is similar. Patients with PAD are less likely to receive combination therapy (n= 12 vs. n=25) and are less likely to have tumor progression on ICI (n=1) compared to those without PAD (n=3). Selection bias is noted in this initial sample since half of recruited patients have PAD. The CanRIO cohort provides valuable insight into real-world spectrum and management of Rh-irAE secondary to immunotherapy for cancer.
Disclosure of Interests Shahin Jamal Grant/research support from: CanRIO has received financial support from BMS and Organon, Lourdes Gonzalez Arreola: None declared, Julia Tan: None declared, Carrie Ye: None declared, Janet Roberts: None declared, Aurore Fifi-Mah: None declared, Marie Hudson: None declared, Sabrina Hoa: None declared, Janet Pope: None declared, Ines Colmegna: None declared, C. Thomas Appleton: None declared
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