Alexandra Ladouceur1, Thomas Barnetche2, Sorilla Mary-Prey3, Caroline Dutriaux4, Emilie Gerard3, Anne Pham-Ledard3, Marie Beylot-Barry3, Maeva Zysman3, Rémi Veillon3, Charlotte Domblides5, Amaury Daste5, Marine Gross-Goupil5, Baptiste Sionneau5, Félix Lefort5, Mathieu Larroquette5, Christophe Richez6, Marie-Elise Truchetet2, Thierry Schaeverbebke7 and Marie Kostine2, 1Department of Rheumatology of McGill University and CHU-Bordeaux, Montréal, QC, Canada, 2Bordeaux University Hospital, Bordeaux, France, 3Department of Dermatology, Bordeaux University Hospital, Bordeaux, France, 4CHU-Bordeaux, Bordeaux, France, 5Department of Medical Oncology, Bordeaux University Hospital, Bordeaux, France, 6Université de Bordeaux, Bordeaux, France, 7University Hospital of Bordeaux, Bordeaux, France
Background/Purpose: Immune checkpoint inhibitors (ICI) are a revolutionary treatment that boost a patient's own immune system to fight cancer. However, activation of the immune system often induces off-target immune-related adverse events (irAEs). ICI-induced inflammatory arthritis (ICI-IA) affects about 5% of ICI recipients and can lead to ICI discontinuation which might potentially negatively affect tumor outcomes. We aimed 1) to characterize the evolution of ICI-IA while ICI treatment is maintained and 2) to assess how ICI-IA influences ICI management across time.
Methods: All ICI-treated patients referred to rheumatology at Bordeaux University Hospital were identified and patients with ICI-IA defined by either the presence of at least one synovitis on physical exam and/or on imaging or polymyalgia rheumatica (PMR)-like symptoms with a follow-up of ≥ 6 months after ICI-IA onset were included. Charts were manually reviewed to extract data on baseline characteristics, investigations, management and both ICI-IA and tumor outcomes.
Results: Out of 281 referred patients, 80 fulfilled the inclusion criteria, of which 49 (61.3%) were male. The median duration follow-up after ICI-IA onset was 108 weeks [ranging from 26-330 weeks]. The most common tumor was melanoma (n=38, 47.5%), followed by lung cancer (n=16, 20.0%). The mean time from ICI-IA onset to ICI-IA treatment was 8.6 weeks and ICI was continued in 63 patients (78.8%) or temporary held in 11 (13.8%). Prednisone was prescribed in 74 patients (92.5%), csDMARDs in 22 (27.5%) and biologics in 2 (2.5%). ICI-IA resolved allowing ICI-IA treatment discontinuation in 27 patients (33.8%) while still being treated with ICI. Among those, 26 (96.3%) were treated with prednisone (median maximal dose 15 mg and median duration 52.0 weeks), 3 (11.1%) with csDMARDs and 1 (3.7%) with biologics. In patients with persistent ICI-IA while on ICI, 20 (40%) and 34 (68%) had resolved at 6 and 12 months post ICI discontinuation, respectively. During follow-up, the main reason for ICI discontinuation was a cancer stable or in remission in 31 patients (38.8%), cancer progression in 22 (27.5%), other irAE in 7 (8.8%) and ICI-IA in 4 (5.0%). Of note, ICI-IA treatment and ICI management were similar between those with active arthritis and those with resolved arthritis at 6 and 12 months post ICI discontinuation.
Conclusion: In this cohort, ICI was safely continued in most patients experiencing ICI-IA. Over one third of ICI-IA resolved despite maintaining active ICI treatment allowing arthritis treatment discontinuation. Larger studies are needed to determine predicting factors of resolving ICI-IA as this could help minimize exposure to immunosuppressive treatment.
A. Ladouceur: None; T. Barnetche: Eli Lilly, 2; S. Mary-Prey: Bristol-Myers Squibb(BMS), 2, 12, Congress fees participation, Merck/MSD, 2, 12, Congress fees reimbursement; C. Dutriaux: Bristol-Myers Squibb(BMS), 1, 2, 12, Clinical trials, travel and accomodation fees, Merck/MSD, 2, 12, Clinical trials, travel and accomodation fees for boards or congress, Novartis, 2, 12, Clinical trials, travel and accomodation fees; E. Gerard: Bristol-Myers Squibb(BMS), 1, 12, Clinical trials, travel to scientific meetings, Merck/MSD, 1, 12, Clinical trials, travel to scientific meetings; A. Pham-Ledard: Bristol-Myers Squibb(BMS), 12, conference participation fees, Merck/MSD, 12, Congress participation fees; M. Beylot-Barry: None; M. Zysman: AstraZeneca, 2, Bristol-Myers Squibb(BMS), 2; R. Veillon: AbbVie/Abbott, 5, Amgen, 6, AstraZeneca, 6, 12, Travel, accomodations, expenses, Bristol-Myers Squibb(BMS), 5, 5, 6, GlaxoSmithKlein(GSK), 5, Janssen, 2, Merck/MSD, 5, Novartis, 5, Roche, 6; C. Domblides: Amgen, 4, 12, travel/congress, AstraZeneca, 1, 12, travel/congress, Bristol-Myers Squibb(BMS), 1, 12, Travel/congress, Janssen, 1, Merck/MSD, 4, 12, Travel/congress, Pfizer, 12, Travel/congress, Roche, 12, Travel/congress; A. Daste: Bristol-Myers Squibb(BMS), 2, Merck/MSD, 2; M. Gross-Goupil: Amgen, 6, Bristol-Myers Squibb(BMS), 1, 6, 12, Clinical research, Merck/MSD, 1, 6, 12, Clinical research, Pfizer, 1, 12, Clinical research, Roche, 12, Clinical research; B. Sionneau: None; F. Lefort: AstraZeneca, 1, 2, 12, Clinical trials, Bristol-Myers Squibb(BMS), 12, Clinical trials, Merck/MSD, 1, 2, 12, Clinical trials, Pfizer, 12, Travel and accomodation fees, Roche, 12, Clinical trials; M. Larroquette: None; C. Richez: AbbVie/Abbott, 2, 6, Amgen, 6, AstraZeneca, 2, 6, Bristol-Myers Squibb(BMS), 6, Eli Lilly, 6, 12, receipt of drugs, GlaxoSmithKlein(GSK), 2, 6, Novartis, 2, 6, Pfizer, 2, 6; M. Truchetet: AbbVie/Abbott, 2, 6, Boehringer-Ingelheim, 2, 6, Gilead, 5, 6, Merck/MSD, 6, UCB, 6, 12, support for conferences; T. Schaeverbebke: AbbVie/Abbott, 1, 6, 12, Clinical trials, Bristol-Myers Squibb(BMS), 1, 1, 6, 6, Eli Lilly, 1, 5, 6, 12, Clinical trials, Janssen, 6, Merck/MSD, 12, Clinical trials, Novartis, 1, 6, 12, Clinical trials, Pfizer, 1, 5, 12, Clinical trials; M. Kostine: None.