[Predictable toxicities with futures immunotherapies or combinations]

Abstract

Immunotherapy by immune check-points inhibitors (ICIs) recently improved many solid tumors survival data. ICIs target and inhibit down-regulation signals between T cells and tumor cells involved in carcinogenesis, in order to enhance anti-tumor immunity. With few years' hindsight of ICIs utilization in daily practice, we learned about their safety profile. By releasing the brakes of the host immune-system, ICIs exposure leads to on-target off-tumor immune related adverse events (IRAEs). Compared to standard chemotherapiy regimens, IRAEs remain rare, but sometimes serious and compromising treatment continuation, mostly despite objective tumor response. Several immunotherapy molecules are currently developed, with various mechanisms of action but always targeting the immune anti-tumor response. New drugs imply new safety profiles, especially since a lot of ongoing clinical trials are assessing combination of multiples drugs. Consequently, a good knowledge and management of these new toxicities will be essential to choose the new therapeutic schedules in many tumor types. Indeed, despite the actual poor prognosis of concerned tumor types, the progressive outcomes improvement implies long-term exposure to treatments. Safety and quality of life under treatment will become key endpoints for therapeutic decision.

Keywords: Auto-immunity; Auto-immunité; Immune checkpoints inhibitors; Immunotherapy; Immunothérapie; Inhibiteurs de point de contrôle immunitaires; Safety; Sécurité; Toxicity; Toxicité.