POS1341\u2005TOCILIZUMAB FOR THE TREATMENT OF IMMUNE-RELATED ADVERSE EVENTS TO IMMUNE CHECKPOINT INHIBITORS: A CASE SERIES

Abstract

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.To evaluate the efficacy and safety of tocilizumab, as monotherapy or alongside the continuation of ICI treatment, in the management of irAEs.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.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.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.[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 1Patient 2Patient 3Patient 4Patient 5Age at irAE onset (years)6952725775SexMaleMaleMaleFemaleFemaleNeoplastic histologyNSCLCNSCLCNSCLCNSCLCPleural mesotheliomaICI treatmentNivolumabNivolumabPembrolizumabPembrolizumabPembrolizumabirAEMyocarditisArthritisCutaneous vasculitisArthritisArthritisLarge vessel vasculitis ICI discontinuation due to irAEYesNoNoNoYes PDN initial dose (mg daily)5037.5252537.5 DMARD therapy *T16: ANKT20: TCZT26: TCZ + MMFT5: MTXT6: MTX + ANKT11: MTX + TCZT3: MTXT11: MTX + TCZT4: MTXT6: MTX + TCZT3: TCZ irAE outcomeImprovementLow disease activityLow disease activityRemissionRemissionFollow-up length (months)Since oncologic diagnosisSince TCZ start50104725572255268Oncological outcomeProgressive disease and deathComplete responseStable diseaseStable diseaseComplete 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.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