Although benefits may exist for specific subgroups, their limited efficacy and increased toxicity highlight the need for future clinical trials that prioritize biomarker-driven designs that test for the expression of different immune checkpoints, Treg abundance and ratios with CD4+/CD8+ effector T cells, markers of pDC activity, and strategic treatment combinations, like combined LAG3, PD-1, and TIGIT inhibition or treatments that target cellular adhesion molecules like VLA-4-mediated drug resistance to define immune checkpoint blockade activity in MM. This evidence concerns the gene CD4 and Miyoshi myopathy.