SAT0594 ADVERSE AUTOIMMUNE EVENTS IN CANCER PATIENTSTREATED WITH IMMUNOTHERAPY. ANALYSIS OF CASES BETWEEN 2011 AND 2018
Authors: Piedad León, Maria Lisbona Muñoz, Marta Mejías, Purificación Estévez, Rosalía Martínez, María Fernández, Clara Aguilera Cros, Ricardo Juan Gil Velez, Alejandro Muñoz, Esteban Rubio Romero, Juan Povedano Gomez
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Immunotherapy has revolutionized the treatment of cancer. The use of checkpoints inhibitors aimed at stimulating the immune system to mediate regression of established malignant tumors has shown a noticeably increase in the last decade. However, immunotherapy has been associated with side effects novel to cancer patients such as immune-related adverse events (IAEs) that can affect any organ or system, either during the course of immunotherapy or once the treatment was completed. <h3>Objectives:</h3> To survey the occurrence and type of AAEs in 190 cancer patients treated with immunotherapy between 2011 and 2018. <h3>Methods:</h3> We surveyed the occurrence of IAEs in cancer patients who received immunotherapy in the Oncology Service at 'Virgen del Rocío' University Hospital (Seville, Spain) between 2011-2018. The types of cancer present in the patients analysed included: non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), melanoma, kidney cancer, bladder cancer and others. The checkpoints inhibitors analysed included Ipilimumab (CTLA-4), Nivolumab (PD-1), Pembrolizumab (PD-1) and Atezolizumab (PD-L1). The nature of IAEs (rheumatic/non-rheumatic), the magnitude of complaint (mild/moderate/severe) and the outcome of patients depending on IAEs management was analysed. Finally, we used a multivariate analysis in search for patterns in IAE occurrence depending on cancer type, patient and treatment factors. <h3>Results:</h3> A total of 190 patients were collected, 143 men and 47 women having NSCLC (51.1%), melanoma (25.3%), kidney cancer (6.8%), bladder cancer (5.3%), SCLC (2.1%) and others. They received immunotherapy with Atezolizumab (15.8%), Ipilimumab (4.7%), Nivolumab (61.1%) and Pembrolizumab (18.4%). Overall, 28 patients (14%) developed an AAE secondary to immunotherapy. Four of them involved rheumatic diseases (1 seronegative polyarthritis, 1 inflammatory myopathy and 2 rheumatic polymyalgia), whereas other non-rheumatic diseases were observed: 13 endocrine (12 thyroiditis and 1 DM type I debut with ketoacidosis), 5 pulmonary (pneumonitis), 3 dermatological (2 atopic dermatitis and 1 psoriasis), 2 digestive (colitis and autoimmune pancreatitis) and 1 neurological (hypophysitis). The drug that showed the highest occurrence of IAEs was Nivolumab (30%). In these patients, IAEs were associated with a median number of cycles of 7 (Q<sub>1</sub> = 4, Q<sub>3</sub> = 17.7, non-parametric data, Shapiro-Wilk test, p &lt;0.0001). Mild adverse events occurred in 60% of patients with IAEs, for which immunotherapy was not suppressed. However, the medication was suppressed in the remaining 40% of the cases. Exceptionally, one patient underwent a severe IAE (pneumonitis) that resulted in death. In terms of the occurrence of IAEs, there was no difference between sexes (men 6.3%, women 6.4%). The rheumatic IAEs responded well to treatment with corticosteroids without further biological treatments or DMARDs. <h3>Conclusion:</h3> Immunotherapy is changing the typology of side effects in cancer patients, including IAEs. The cases analysed showed a relatively small number of rheumatic events that were easily solved with corticosteroids (nor the immunotherapy treatment was suppressed or immunosuppressive treatment was necessary). The study highlights the benefits of involving multidisciplinary medical teams to manage oncologic patients treated with immunotherapy towards the early detection and treatment of IAEs. <h3>References</h3> [1] Michael A. Postow, M.D., Robert Sidlow, M.D., and Matthew D. Hellmann, M.D. Immune-Related Adverse Events Associated with Immune Checkpoint BlockadeN Engl J Med 2018; 378:158-168. DOI: 10.1056/NEJMra1703481 <h3>Disclosure of Interests:</h3> None declared