Journal
EUROPEAN JOURNAL OF CANCER
Volume 82, Issue -, Pages 34-44Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.ejca.2017.05.032
Keywords
Immunotherapy; Connective tissue diseases; Rheumatic diseases; Immune thrombocytopenia
Categories
Funding
- BMS
- MSD
- Roche
- AMGEN
- Novartis
- AstraZeneca
- Astex
- Covagen
- Clovis
- GSK
- Gammamabs
- Lilly
- Mission Therapeutics
- Merus
- Pfizer
- Pierre Fabre
- Roche-Genentech
- Sanofi
- Servier
- Takeda
- BMS France
- Genzyme
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Aim: The growing use of immune checkpoint inhibitors (ICIs) is associated with the occurrence of immune-related adverse events (irAEs). Few data are published on systemic, immunohaematological and rheumatic irAEs. In a pharmacovigilance database analysis, we screened for these irAEs and calculated their prevalence. Patients and methods: Participants were recruited via Registre des Effets Indesirables Severes des Anticorps Monoclonaux Immunomodulateurs en Cancerologie (REISAMIC)(1) a French registry of grade >= 2 irAEs occurring in ICI-treated patients. The pathologies of interest were systemic autoimmune and inflammatory diseases, rheumatic diseases and immune cytopenia. Results: Out of 908 patients treated with anti-Programmed cell Death 1 (PD1)/anti-Programmed cell Death-Ligand 1 (PD-L1) agents (together with an anti-cytotoxic T-lymphocyte antigen-4 (CTLA-4) agent in 40 cases) between December 2012 and December 2016 at a single centre, 21 patients experienced systemic irAEs. The types and the prevalence of irAEs were as follows: immune thrombocytopenia (0.2%), Sjogren syndrome (0.3%), rheumatoid arthritis (0.2%), polymyalgia rheumatica (0.2%), psoriatic arthritis (0.2%), seronegative polyarthritis (0.7%) and sarcoidosis (0.2%). Patients with Sjogren syndrome or seronegative polyarthritis were more likely to have received combination therapy with ipilimumab (2.5% for both). We described these 21 cases, together with nine additional cases from five other centres. Most irAE were moderately severe (grade 2, 63%). The median time to onset was 57 degrees days (interquartile range (IQR) 24-117). The ICI was withdrawn in 12 cases, 25 patients (83%) received corticosteroids, and five patients (17%) received immunosuppressant/immunomodulatory agents. The irAEs resolved fully or partially in 28 cases (93%). Conclusion: Although systemic, immunohaematological and rheumatic diseases are rarely associated with ICI use, the prevalence is higher when two ICIs are combined. Corticosteroids are often effective and may enable the continued administration of ICIs. Studies designed to identify at-risk patients are warranted. (C) 2017 Elsevier Ltd. All rights reserved.
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