CTLA4 and melanoma: In 2014, fully humanized anti-PD-1 mAbs pembrolizumab and nivolumab became the first PD-1 targeted therapeutics approved by FDA for refractory and advanced melanoma.357,372–374 Although anti-PD-(L)1 therapy entered the market later than anti-CTLA-4 therapy, PD (L)-1 blockade have shown broader clinical utility than anti-CTLA-4 treatment.