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What do we know about cancer immunotherapy? Long-term survival and immune-related adverse events

D errico G, Miranda J, Ostios L, Villamayor J

Immunotherapy delivered a new therapeutic option to oncologist: Ipilimumab (anti-CTLA-4), Nivolumab and Pembrolizumab (anti-PD1) and Atezolizumab (anti-PD-L1) increase overall survival and show a better safety profile compared to chemotherapy in patients with metastatic melanoma, lung, renal cancer among others. But all that glitters is not gold and there is an increasing number of reports of adverse effect while using Immune-checkpoint inhibitors. While chemotherapy could weaken the immune system, this novel immunotherapy could hiper-activate it, resulting in a unique and distinct spectrum of adverse events, called Immunes-related adverse events irAEs. irAEs ranging from mild to potentially lifethreatening events can involve many systems, and their management is radically different from that of cytotoxic drugs: immunosuppressive treatments, such as corticoids, infliximab or mycophenolate mofetil usually results in complete reversibility, but failing to do so can lead to severe toxicity or even death. Patient selection is an indirect way to reduce adverse events minimizing the number of subjects exposed to this drugs: unfortunately PDL-1, the actual predictive biomarker wouldn’t allow clinicians select or exclude patients for treatment with checkpoint inhibitors.