For example, in subjects with melanoma, the treatment combination of anti-PD-1 and anti-CTLA-4 blockade led to significantly more adverse events compared to anti-PD-1 monotherapy (55–60% vs. 10–20% high-grade), where nearly 80% of subjects treated with the combination therapy discontinued therapy as a result of toxicity [56, 57]. This evidence concerns the gene PDCD1 and melanoma.