The 2016-2019 ImmunoTOX Assessment Board Report: Results from a Descriptive Real-Life Study of a Collaborative Management of Immune-Related Adverse Events Induced by Immune Checkpoint Inhibitors

Abstract

Background: Although immunotherapy is globally better tolerated than chemotherapy, immune checkpoint inhibitors may be associated with immune-related adverse events (irAEs) characterized by their diversity, unpredictability, and corticosteroid responsiveness. We investigate the ImmunoTOX meeting's activities, a multidisciplinary real life and case-by-case approach to manage irAEs, to capture the salient medical needs in the management immunological toxicities. Methods: The ImmunoTOX assessment board is an academic, multidisciplinary group of oncologists and organ specialists that was set up in April 2016 at Gustave Roussy cancer centre in France. It meets every two weeks to discuss the case-by-case management of patients presenting with irAEs. This report describes ImmunoTOX's meeting activities between April 6th, 2016, and January 2nd, 2019. Findings: Over the 32 months of study period, 398 requests concerning 356 patients were submitted to the ImmunoTOX board. The most common tumour types of patients were thoracic cancers (n=105, 29%), skin cancers (n=82, 23%), and renal carcinomas (n=28, 8%). The requests most frequently asked were causal link between immunotherapy and adverse event, (n=148, 37%), the possibility for retreatment after hold due to previous adverse event (n=109, 27%), the clinical management of complex situation (n=100, 25%), and the initiation of immunotherapy in patients with pre-existing comorbidities (n=41, 10%). The ImmunoTOX board found a relationship between immunotherapy and adverse event in 273 (77%) of the 356 patients. The organ systems most frequently involved by irAEs were the lung (n=58, 21%), gastrointestinal tract (n=36, 13%), liver or biliary tract (n=33, 12%), musculoskeletal system (n=27, 10%) and nervous system (n=23, 8%). The retreatment by immunotherapy after holding due to previous adverse event and the initiation of immunotherapy in patients with pre-existing autoimmune comorbidities, were assessed as precaution for use and not formally contraindication in 65% and 93% of the cases, respectively. Interpretation: The medical needs in the management of immune-related adverse events involve five salient organ systems, namely the lung, gastrointestinal, liver and biliary tract, musculoskeletal and nervous systems. Retreatment after holding due to previous adverse events and immunotherapy initiation in patients with autoimmune comorbidities were mostly assessed as precaution for use and not formal contraindication. A multidisciplinary and case by case approach can be helpful and complementary of general guidelines in the management of immunological toxicities. Clinical Registration Number: The study was registered with the French National Data Protection Commission (Commission Nationale de l’Informatique et des Libertes; reference: 2098694v0). Funding Statement: Gustave Roussy and the Gustave Roussy Immunotherapy Programme. Ethical Approval Statement: All the patients gave their verbal, informed consent to the publication of their anonymized data, and the study was approved by the institutional review board at Gustave Roussy (Villejuif, France).