A. Cottu1, L. Delaval2, A. Forestier3, A. Tomelleri4, C. Campochiaro, M. Bond5, J. Dion6, A. Gury7, X. Savary8, R. Dhote9, A. Betrains10, L. Bouillet11, E. Liozon12, E. Bories13, A. Petitdemange1, P. Legendre14, B. Crichi15, P. Kerschen16, L. Carneiro Esteves17, G. Armengol18, R. Outh19, O. Al Tabaa20, L. Wolff21, M. Ilzkovitz21, M. Cherif21, L. Dagna4, P. Bruneval22, B. Terrier1
1National Referral Center for Rare Systemic Autoimmune Diseases, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris (AP-HP), Department of Internal Medicine, Paris, France
2Saint-Denis Hospital, Saint-Denis, France
3Centre Oscar Lambret, Lille, France
4Unit of Immunology, Rheumatology, Allergy and Rare Disease, IRCCS San Raffaele Hospital, Milan, Italy
5Department of Rheumatology, Hospital of Bruneck (ASAA-SABES), Teaching Hospital of the Paracelsius Medical University, Brunico, Italy
6Department of Internal Medicine, Toulouse University Hospital Oncopole, Toulouse, France
7Department of Internal Medicine, Arras GHAT, Arras, France
8Department of Internal Medicine, Brest CHU Hospital, Brest, France
9Department of Internal Medicine, Centre Hospitalier Avicenne, Bobigny, France
10Department of General Internal Medicine, University Hospitals Leuven, Leuven, Belgium
11Internal Medicine Department, Grenoble University Hospital, Grenoble, France
12Department of Internal Medicine, University Hospital of Limoges, Limoges, France
13Department of Internal Medicine, Purpan CHU Hospital, Toulouse, France
14Department of Clinical Immunology, Centre Hospitalier du Mans, Le Mans, France
15Department of Internal Medicine, Saint Louis Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France
16Department of Neurology, Luxembourg Hospital Center, Luxembourg city, Luxembourg
17Department of Internal Medicine, Centre Hospitalier Universitaire de Saint-Etienne, Saint-Etienne, France
18Clinique Saint-Hilaire, Rouen, Rouen, France
19Internal Medicine Department, Perpignan Hospital Center, Perpignan, France
20Department of Rheumatology, Hôpital NOVO, Pontoise, France
21Department of Internal Medicine, Hôpitaux Universitaires de Bruxelles, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium
22Department of Pathology, Georges-Pompidou European Hospital, AP-HP, Paris, France
Background: Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment but frequently cause immune-related adverse events (IrAEs). Vasculitis, including large vessel vasculitis (LVV), is a recognized but rarely reported IrAE.
Objectives: We aimed to describe and compare clinical characteristics and evolution of ICI-induced LVV to primary LVV.
Methods: This retrospective, multicenter European (France, Italy, Belgium, Luxembourg) study included adult patients who developed LVV after ICI therapy between March 2018 and August 2024. Patients were compared to four matched controls with primary LVV. LVV was defined histologically and/or morphologically. The primary endpoint was the achievement of a sustained remission defined as the resolution of specific symptoms and inflammatory markers without relapse at the end of follow-up.
Results: Of the 27 patients included (median [IQR] age 68 [61–74]), 5 (19%) had a history of polymyalgia rheumatica or giant cell arteritis. Median time from ICIs initiation to LVV diagnosis was three [2–17] months. Eight patients (30%) received ipilimumab-nivolumab combination therapy, all of whom developed LVV within six months. Most clinical features were similar to controls, however PET-scan diagnosis and large-vessel involvement were more frequent in ICI-induced LVV. Visual loss occurred in four (15%) patients. Management included discontinuation of ICIs in 19 (70%) patients and administration of glucocorticoids in most cases. After a median follow-up of 12 [5–20] months, 20 (74%) achieved sustained remission. Relapse or treatment failure of LVV occurred in 3/9 (33%) patients who continued ICIs and 4/18 (22%) who discontinued them. By last follow-up, nine (33%) patients had died, mainly from cancer (n=8).
Conclusion: ICI-induced LVV is a rare, early-onset IrAE. Although continuation of ICIs may affect LVV outcomes, cancer progression remains the primary cause of mortality, highlighting the need for balanced therapeutic approaches.
