Basically, this report describes a first attempt to develop a standardized (i.e., irrespective to patients’ HLAs and to patient-specific MMAA expression profiles), easy-to-perform, and feasible (such as ELISpot-based assay on PB samples) multi-antigenic myeloma-specific immunoassay (here referred to as “MaMs” T-cell assay), which could act as innovative prognostic tool, helping to predict different evolutions of monoclonal gammopathies. Here, HLA-S is linked to plasma cell myeloma.