IMMUNE MEDIATED ADVERSE DRUG REACTIONS TO ICI TREATMENT.A REAL CLINICAL CASE STUDY

Abstract

Immunotherapy, in particular checkpoint inhibitors (ICIs), has established itself as the standard of care for solid tumors due to its proven efficacy and improved patient prognosis. The main classes of ICIs include PD-1/PD-L1 inhibitors (e.g. pembrolizumab, nivolumab, durvalumab) and CTLA-4 inhibitors (e.g. ipilimumab). As indications and combination regimens have increased, so has the incidence of immune-mediated adverse events (irAEs), which can affect almost any organ. irAEs vary in severity and time of onset from early to late, recurrent, chronic or polyorganic. The mechanisms behind them include T-cell overactivation, elevated cytokine levels and the role of the gut microbiota. CTLA-4 inhibitors are associated with higher toxicity (up to 24% high grade) and combinated immunotherapy – with the highest incidence (up to 59%). According to the SITC consensus, tracking and defining irAEs is important for clinical practice. Ipilimumab and nivolumab remain the main agents included in combinated regimens, such as the one in the CheckMate 9LA trial, where the combination of nivolumab, ipilimumab and chemotherapy improved survival over chemotherapy alone – independent of PD-L1 expression. Precise management of irAEs and individualization of therapy are key to maximizing the clinical benefit of immunotherapy.