In a meta-analysis of 112 trials including 19,217 patients, IRAE-associated fatality rates ranged between 0.36% for anti-PD-1 mono-therapy and 1.23% for PD1/PD-L1 plus CTLA-4 combinational therapy and were most commonly caused by colitis, pneumonitis, hepatitis, myocarditis and neurotoxic effects (145). This evidence concerns the gene PDCD1 and myocarditis.