LAUSR

Abstract Background The adverse events generated by immunotherapies are characterized by their wide diversity, unpredictability and reversibility by steroid used, and requires a delicate management. A collaborative organization of immunological toxicology management called ImmunoTOX (iTox) has been set up at Gustave Roussy to support physicians in their routine practice. Methods Descriptive study of all consecutive advice given by the ImmunoTOX committee at Gustave Roussy from Apr 6, 2016 to Jan 2, 2019. The iTox committee organizes a multidisciplinary meeting twice a month with organs specialists, oncologists, pharmacovigilants, radiologists, around prescribing physicians facing difficult to manage or unusual immune related adverse events (irAEs). Results The iTox committee delivered 398 pieces of advice for 356 patients (207 men and 149 women) receiving immunotherapies. Patients received anti-PD1 (55%) or anti-PDL1 (6%) given in monotherapy, or in combination with anti-CTLA4 (11%), or in combination with targeted therapy (11%), or another immunotherapy regimen (17%). The queries patterns for advices questioned the causal link (37%), rechallenge over G ≥ 3 (27%), or a complex clinical management (25%) or the possibility of initiating immunotherapy in a patient with comorbidities (10%). The iTox committee retained a causal link between the adverse event and immunotherapy in 273 of the 356 patients (77%). Of these 273 patients with irAEs, the grade of maximum severity was grade 1-2 in 112 (41%), grade 3-4 in 148 patients (54%), and irAE ultimately resulted in death in 13 (5%) patients. The organ categories mostly involved by requests were lung (21%), gastrointestinal (13%), liver (12%), musculoskeletal (10%) and neurological (8%). Over the study period, the 273 patients with irAEs led to 313 requests for advice that recommended systemic corticosteroids (n = 193, 62%) or a second immunomodulatory agents (n = 45, 14%). Conclusions These results should help cancer hospitals to further appreciate the current medical needs in their management of irAEs. By a specific management, patients with autoimmune comorbidities and rechallenge over G ≥ 3 could be regarded as precautions for use and not absolute contraindications. Clinical trial identification Commission Nationale de l’Informatique et des Libertes N°2098694v0. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure J. Michot: Advisory / Consultancy: BMS; Advisory / Consultancy: Pfizer; Honoraria (self), Honoraria (institution), Advisory / Consultancy: Cellgene; Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Roche; Honoraria (institution): Abbvie; Honoraria (institution): Xencor. J. Soria: Full / Part-time employment: MedImmune. C. Massard: Honoraria (institution), Advisory / Consultancy: BMS; Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Honoraria (institution), Advisory / Consultancy, Leadership role: Lilly. All other authors have declared no conflicts of interest.