Focusing back to PD-L1/PD-1 distribution among patients at different stages of disease, the similarities between patients with asymptomatic and active myeloma, together with the highly compromised BM microenvironment of relapsed MM patients, potentially suggest that SMM patients could benefit from PD-L1/PD-1 blockade, more than MMR which are currently the main candidates for anti-PD-L1/PD-1 treatment. This evidence concerns the gene CD274 and plasma cell myeloma.