Fanny De La Fuente1, Rakiba Belkhir2, Julien Henry3, Chi Duc Nguyen4, Thao Pham5, Vincent GERMAIN6, Pierre-Edouard Gavand7, Céline Labadie1, Claire Brière8, Ambre Lauret8, Thierry Cardon9, Gaël Mouterde10, Isabelle Bonnet11, Léa Rouxel12, Marie Truchetet1, Thierry schaeverbeke13, Christophe Richez14 and Marie Kostine15, 1Bordeaux University Hospital, Bordeaux, France, 2Rheumatology departement, Bicêtre, Paris-Saclay university, Le Kremlin Bicêtre, France, 3Department of Rheumatology, University Paris-Saclay, Hospital Bicêtre, Le Plessis Robinson, Ile-de-France, France, 4Bethune Hospital, Bethune, France, 5Aix-Marseille univ, APHM, Marseille, France, 6Pau Hospital, Rheumatology, Pau, France, Pau, France, 7Rhena Clinic, Strasbourg, France, 8Intercommunal Creteil Hospital, Créteil, France, 9Lille University Hospital, Lille, France, 10Lapeyronie Hospital, Montpellier, France, 11University Paris-Saclay, Hospital Bicêtre, Bicêtre, France, 12Arcachon Hospital, Arcachon, France, 13CHU de Bordeaux, Bordeaux, France, 14Université de Bordeaux, Bordeaux, France, 15Pellegrin Hospital, University Hospital of Bordeaux, Rheumatology, Bordeaux, France
Background/Purpose: Rheumatic immune related adverse events (irAEs) are observed in about 5 to 10% of cancer patients receiving checkpoint inhibitors (ICIs), with inflammatory arthritis (IA) and polymyalgia-rheumatica (PMR) as frequent clinical presentations. Although most patients experiencing rheumatic irAEs respond well to low-to-moderate dose of prednisone allowing ICI continuation, few patients require treatment escalation with conventional and/or biological DMARD owing to severe irAE or as glucocorticoids-sparing strategy. Since few data are available regarding the use of bDMARDs and tsDMARDs in this setting, we aimed to assess their efficacy and tolerance in patients with rheumatic irAEs.
Methods: the Club Rhumatisme and Inflammation (CRI) french network, we conducted a multicenter, retrospective, observational study of cancer patients diagnosed with rheumatic irAE under ICI(s) and treated with bDMARD or tsDMARD. Clinical data were collected using a standardized case report form.
Results: Twenty-one patients (62% men) were included, with a median age of 54 years and a diagnosis of lung cancer (n=11), melanoma (n=8), renal carcinoma (n=1) or lymphoma (n=1). All patients were receiving an anti PD-1, in combination with an anti CTLA-4 for 2 patients. The median time between ICI initiation and the rheumatic irAE onset was 22 weeks, ranging from 1 to 156 weeks. All but one had inflammatory arthritis with RA-like (n=16), PMR-like (n=2) or psoriatic arthritis-like (n=2) phenotype, and one patient had fasciitis. 90% were treated with glucocorticoids as first-line therapy and 71% received methotrexate before the bDMARD or tsDMARD. Anti-IL6R therapy was used in 13 patients (62%), leading to clinical improvement in 85 but one patient experienced intestinal perforation and cancer progression was noticed in 46% of patients. TNF inhibitors was used in 5 patients (24%), with 60% efficacy, but two infections (diverticulitis and pneumonitis) reported and cancer progression observed in 60%. Baricitinib was used in one RA-like patient with irAE resolution but cancer progression after 18 months. Ustekinumab was successfully used in one PsA patient. Short course of anakinra had no effect on both irAE and cancer. One patient experienced myofasciitis, associated with scleroderma reaction and peripheral neuropathy and was treated with rituximab with partial improvement and cancer remission up to one year. ICI was discontinued due to the rheumatic irAE in 52% of patients, temporarily (n=4) or permanently (n=7). Glucocorticoids were stopped (27%) or reduced (38%) following bDMARD/tsDMARD initiation. The bDMARD was discontinued in 8 patients after improvement or resolution of the irAE, with only one patient experiencing a flare. At the last follow-up, 8 patients were still receiving the bDMARD with ongoing tumor response.
Conclusion: Anti-IL6R therapy was mostly and safely used in severe rheumatic irAE with insufficient response to glucocorticoids and methotrexate, with improvement in >80% of patients. TNFi appeared slightly less effective. Overall, cancer progression occurred in about half of patients and whether the bDMARD/tsDMARD impacted the tumor response remains to be determined.
Disclosures: F. De La Fuente, None; R. Belkhir, None; J. Henry, None; C. Nguyen, None; T. Pham, None; V. GERMAIN, None; P. Gavand, None; C. Labadie, None; C. Brière, None; A. Lauret, None; T. Cardon, None; G. Mouterde, None; I. Bonnet, None; L. Rouxel, None; M. Truchetet, AbbVie/Abbott, Pfizer, Eli Lilly, Galapados; T. schaeverbeke, None; C. Richez, AbbVie/Abbott, Amgen, AstraZeneca, Biogen, Bristol-Myers Squibb(BMS), Galapados, GlaxoSmithKlein(GSK), Eli Lilly, Novartis, Pfizer; M. Kostine, Bristol-Myers Squibb(BMS), Merck/MSD, Novartis, Janssen, Biogen.
