POS1341 TOCILIZUMAB FOR THE TREATMENT OF IMMUNE-RELATED ADVERSE EVENTS TO IMMUNE CHECKPOINT INHIBITORS: A CASE SERIES
Authors: C. Campochiaro, N. Farina, A. Tomelleri, G. De Luca, G. Cavalli, C. Lazzari, R. Ferrara, M. Garassino, V. Gregorc, L. Dagna
Journal: Annals of the Rheumatic Diseases (2021)

Background: Immune checkpoint inhibitors (ICI) are pharmacological agents effectively used in the treatment of several malignant tumors. The hyperactivation of the immune system induced by ICI may trigger an inflammatory involvement of healthy tissues, a phenomenon referred to as immune-related adverse event (irAE). No clinical trials are available to guide the management of irAEs. Observational data suggest tocilizumab might be effective in severe cases of irAEs, but data are scant. The possibility of continuing ICI treatment despite the development of irAE and the subsequent initiation of tocilizumab has never been evaluated. Objectives: To evaluate the efficacy and safety of tocilizumab, as monotherapy or alongside the continuation of ICI treatment, in the management of irAEs. Methods: We retrospectively identified patients who developed irAEs and were referred to our specialized Clinic between May 2018 and December 2020. Among these patients, we identified those who had been treated with tocilizumab and collected information about their oncologic history and outcome, ICI therapy and irAEs. Results: Thirty-nine patients were referred to our outpatient Clinic following the development of irAEs. Five of them were treated with tocilizumab. Disease and demographic features are reported in Table 1. At irAEs onset all patients were treated with glucocorticoids. A steroid-sparing agent was started to permit an adequate prednisone tapering without the irAE relapsing. Before tocilizumab start, two patients were treated with methotrexate monotherapy, one with anakinra monotherapy, and one with methotrexate and anakinra combination therapy. A significant therapeutic effect was confirmed in all patients and no significant adverse reactions were reported. ICI therapy was permanently discontinued in two patients. In the other three cases, cancer immunotherapy was safely continued alongside tocilizumab without further irAEs occurring. Only one patient experienced tumor progression two years after ICI suspension and subsequently died despite the improvement of his myocardial inflammatory involvement. Conclusion: In our cohort, tocilizumab proved to be an effective and safe therapy for the management of irAEs. Our case series also supports the possibility of maintaining ICI while introducing tocilizumab for irAE treatment. This combined approach might represent a suitable therapeutic option to guarantee a significant anti-inflammatory activity without losing the oncologic response. References: [1]Kostine M et al , Ann Rheum Dis, 2021;80:36-48. Table 1. Clinical characteristics of patients who developed irAEs secondary to ICI therapy and who received tocilizumab. Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 Age at irAE onset (years) 69 52 72 57 75 Sex Male Male Male Female Female Neoplastic histology NSCLC NSCLC NSCLC NSCLC Pleural mesothelioma ICI treatment Nivolumab Nivolumab Pembrolizumab Pembrolizumab Pembrolizumab irAE Myocarditis Arthritis Cutaneous vasculitis Arthritis Arthritis Large vessel vasculitis ICI discontinuation due to irAE Yes No No No Yes PDN initial dose (mg daily) 50 37.5 25 25 37.5 DMARD therapy * T16: ANK T20: TCZ T26: TCZ + MMF T5: MTX T6: MTX + ANK T11: MTX + TCZ T3: MTX T11: MTX + TCZ T4: MTX T6: MTX + TCZ T3: TCZ irAE outcome Improvement Low disease activity Low disease activity Remission Remission Follow-up length (months) Since oncologic diagnosis Since TCZ start 50 10 47 25 57 2 25 5 26 8 Oncological outcome Progressive disease and death Complete response Stable disease Stable disease Complete response * Treatment chronology is referred to as a T followed by the number of months since irAE onset. ANK, anakinra; ICI, immune checkpoint inhibitor; irAE, immune-related adverse events; DMARD, disease modifying anti-rheumatic drug; MTX, methotrexate; NSCLC, non-small cell lung cancer; PDN, prednisone; TCZ, tocilizumab. Disclosure of Interests: Corrado Campochiaro Speakers bureau: Novartis, Pfizer, Roche, GSK, SOBI, Nicola Farina: None declared, Alessandro Tomelleri: None declared, Giacomo De Luca Speakers bureau: SOBI, Novartis, Celgene, MSD, Pfizer, Giulio Cavalli Speakers bureau: SOBI, Chiara Lazzari: None declared, Roberto Ferrara: None declared, Marina Garassino: None declared, Vanesa Gregorc: None declared, Lorenzo Dagna Speakers bureau: Abbvie, Amgen, Biogen, BMS, Celltrion, Novartis, Pfizer, Roche, SG, SOBI, Celgene Janssen, MSD, MP