Immunotherapy is a therapeutic strategy aimed at inducing the immune system to identify and combat cancer cells and, alongside the evident clinical success observed in many patients, a specific toxicity profile has emerged, associated with the modulation of the immune system achieved with this type of drugs, known as Immune-Related Adverse Events (irAEs). irAEs encompass a highly heterogeneous spectrum of autoimmune manifestations that can potentially involve any organ or system, occurring in \~ 80% of patients treated with anti-CTLA-4 agents and in \~ 60-70% of patients treated with PD-1/PD-L1 inhibitors. However, severe (grade 3-4) irAEs affect only \~ 15% of patients treated with CTLA-4 inhibitors and \~ 5-10% of patients receiving anti-PD-1/PD-L1 agents, with a mortality rate ranging from 0.36% to 1.23%. The main characteristic of irAEs is their unpredictability in terms of time of onset, severity and responsiveness to immunosuppressive agents. Therefore, the management of irAEs often requires clever interpretation of clinical symptoms, proper choice of laboratory tests and imaging tools, and ability to perform differential diagnosis with other condition associated to tumour itself or to unrelated concomitant events (i.e., infections). Although international societies (i.e.; ESMO) have provided detailed guidelines for the management of irAEs or algorithms for the administration of ICI in patients with pre-existing autoimmune disease, they are sometimes difficult to be applied to certain complex situations. Furthermore, given the scarcity of data from clinical trials, some of these recommendations are mainly based on highly heterogeneous patients' population included in relatively small real world studies. Therefore, recommendations should always be adapted to specific clinical conditions and challenges. Studies investigating these aspects have particularly focused on the autoimmune antibody response, correlating its positivity in various ways with clinical outcomes. However, the results across different studies are not consistent. Moreover, additional prospective data are needed to confirm which information can guide the management of irAEs in order to optimize therapy and improve prognosis without negatively impacting oncological outcomes. The adoption of a therapeutic strategy tailored to irAEs is essential for improving both the immunological and oncological prognosis of patients affected by this group of manifestations. A prospective and cross-sectional observational approach to study irAEs is fundamental to the development of such therapeutic innovation. This study approach must be based not only on monitoring patients who have already developed irAEs but also on profiling patients even before the development of irAEs to determine which factors are associated with this group of pathologies and the different characteristics they may assume once they arise. The protocol will be based on the retrospective acquisition of data concerning the clinical history of the patients involved, from birth until recruitment into the study, and the prospective recording of information regarding the disease characteristics (both immuno-rheumatological and oncological) and the subsequent evolution of the clinical picture. Study procedures will take place during visits scheduled as part of routine clinical practice and will include the collection of data-clinical, laboratory, and imaging-related to the patient's oncological disease and irAEs, the characteristics of the diagnostic-therapeutic procedures performed, and the subsequent immuno-oncological outcomes. All patients scheduled to begin immunotherapy treatment will be enrolled in the study, as well as those who have developed irAEs without being enrolled prior to the onset of immuno-mediated manifestations. Enrolled patients who do not develop irAEs will be considered as the control group, providing essential information on risk profiling for the development of irAEs.
See this in plain English?
AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.
Incidence and characterization of irAEs, from diagnosis to treatment
Timeframe: Data will be collected at baseline, at the onset of irAEs, and at their resolution. Survival and response to oncological treatment will be updated throughout patient follow-up until study completion, with the registry planned to run for 20 years.