FRI0612 IMMUNE-RELATED ADVERSE EVENTS ASSOCIATED WITH IMMUNOTHERAPY. LONG-TERM FOLLOW-UP OF 102 PATIENTS FROM A REFERRAL SINGLE CENTER

Abstract

Background Immune checkpoint blockade therapy (ICBT) has shown remarkable benefit in different cancer types. Blockade of intrinsic down-regulators of immunity increases the activity of the immune system, which can lead to different immune-related adverse events (irAEs). Our aim was to assess the immune-related adverse events in patients who received anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4), anti-programmed cell death 1 (PD-1) or anti-programmed cell death ligand 1 (PD-L1). Objectives Our aim was to assess the incidence, treatment and evolution of irAEs due to ICBT. Methods We set up an observational study of patients treated with Nivolumab and Pembrolizumab (anti-PD1), Atezolizumab (anti-PD-L1) and Ipilimumab (antiCTLA-4) for solid organ tumors. All these patients were followed in a single reference University Hospital from March-2015 up to December-2018. The main outcome was to determinate the incidence of irAEs. Results We studied 102 patients (63♂/39♀) with a mean age of 60.6±9.7 with lung (n=63), melanoma (21), kidney (11), gastric (3), bladder (1), and colon cancer (n=3). Only 7 patients had a previous diagnosis of an immune-mediated disease: psoriasis (n=2), psoriatic arthritis (1), systemic lupus erythematosus (1), spondyloarthitis (1), rheumatoid arthritis (1) and skin lupus (1). ICTB was performed as follows: nivolumab (n=52), pembrolizumab (35), atezolizumab (10) and ipilimumab (5). After a median of 5 [2.5-10.5] months since the ICBT onset, we observed 87 (85.3%) patients with different irAEs, summarized in TABLE. ICBT discontinuation was required in 39 patients. 36 patients received specific treatment (prednisone, antihistamine, levothyroxine and thiamazol), obtaining a good response in 31 cases (79.5%). ICBT was reintroduced in 28 patients (71.8%) after resolution of the adverse event, with an appropriate tolerance in all cases. Gastrointestinal irAEs were the most frequent (n=39, 41.1%), with severe manifestations in 4.9% of the patients. Among these 39 patients, only 11 of them required specific treatment, with oral prednisone in all cases. The diagnosis of gastrointestinal irAEs was based on the clinical manifestations and the laboratory tests. The cutaneous most frequent irAE was rash (n=7, 6.8%), followed by vitiligo (n=2, 1.9%). 15 patients developed a rheumatological irAE (14 arthralgias/arthritis and 1 aortitis). Patients who developed any type of irAE had a better answer to ICBT (70.1%) than those who did not (20%). Conclusion In our study, the majority of autoimmune side effects due to ICBT were gastrointestinal, thyroiditis and rheumatological. The develop of any irAE could be an indicator of good response to ICBT. Disclosure of Interests Lara Sanchez Bilbao: None declared, Inigo Gonzalez-Mazon: None declared, Jose Luis Martin-Varillas: None declared, Marina Delgado Ruiz: None declared, Isabel Bernat Pina: None declared, Belen Atienza-Mateo: None declared, D. Prieto-Pena: None declared, Monica Calderon-Goercke: None declared, Almudena Garcia Castano: None declared, Ricardo Blanco Grant/research support from: Abbvie, MSD, and Roche, Consultant for: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen, Speakers bureau: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen, Miguel A Gonzalez-Gay Grant/research support from: Prof. MA Gonzalez-Gay received grants/research supports from Abbvie, MSD, Jansen and Roche., Speakers bureau: Consultation fees/participation in company sponsored speaker’s bureau from Pfizer, Lilly, Sobi, Celgene, Novartis, Roche and Sanofi.