OP0088 Immune-related adverse events of cancer immunotherapy – when inflammatory side effects are associated with survival: a single-centre prospective cohort study
Authors: M. Kostine, E. Mauric, L. Rouxel, T. Barnetche, R. Veillon, F. Martin, C. Dutriaux, L. Dousset, A. Pham-Ledard, S. Prey, M. Beylot-Barry, A. Daste, M. Gross-Goupil, J. Lallier, A. Ravaud, E. Forcade, B. Bannwarth, M.-E. Truchetet, C. Richez, N. Mehsen-Cetre, T. Schaeverbeke
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Immune checkpoint inhibitors (ICI) represent a new standard of care for the treatment of selected advanced cancers and are still being investigated in many other tumour types. By enhancing the T-cell activation, a unique spectrum of inflammatory side effects has emerged, also known as immune-related adverse events (irAEs), including various well-described rheumatic manifestations. Data regarding the association between irAEs and patient outcomes are conflicting. <h3>Objectives</h3> To evaluate the incidence and characteristics of irAEs in patients receiving ICI, as well as the correlation with tumour response and patient survival. <h3>Methods</h3> This was a single-centre prospective observational study including all cancer patients receiving ICIs. The occurrence of irAEs, tumour response and patient outcomes were assessed on a regular basis. Overall survival has been considered from the start of ICI. <h3>Results</h3> From May 2015 to September 2017, 636 patients (70% male, mean age 64 years) have been included in this cohort while receiving anti PD-1 (n=435), anti PD-L1 (n=66) or anti CTLA-4 (n=3) as single agent or as sequential (n=100) or combined (n=32) therapies. Cancer types were mainly melanoma (n=293), non-small cell lung cancer (n=150) and renal carcinoma (n=83). Overall, 274/633 patients (43%) experienced irAEs, either 1 irAE (n=162), 2 irAEs (n=78) or ≥3 irAEs (n=34), with a median exposure time of 52 days<sup><sup>30–91</sup></sup> for the first irAE. Dermatological irAEs were by far the most frequent (n=160), followed by digestive (n=80), endocrine irAEs (n=67), rheumatic (n=49) and pulmonary irAEs (n=17). So far, evaluation of tumour response was available for 551 patients, including 190 responders (complete response n=36 and partial response n=154), 192 patients with stable disease and 169 with progressive disease. 122/189 responders (65%) and 107/192 with stable disease (56%) experienced at least one irAE while reported only in 40/169 non responders (24%). Patients experiencing at least one irAE had an increased overall survival (median of 1169 days versus 224 days, p&lt;0,0001, figure 1), without statistical difference according to organ system. Of note, there was also no statistical difference regarding tumour response or irAEs occurrence among the 9.4% of patients with preexisting inflammatory or autoimmune disease (60/636). <h3>Conclusions</h3> Although irAE occurrence is not required for treatment benefit, it strongly associates with overall survival. Optimal multidisciplinary management of irAEs, including rheumatologists when needed, is worthwhile to maintain beneficial responses. <h3>Disclosure of Interest</h3> None declared