The present invention provides methods for determining the level or status of minimal residue disease (MRD) in a multiple myeloma (MM) patient including analyzing peripheral natural killer (NK), NK-T and T cell distribution and/or activation, and quantifying inflammatory cytokines, chemokines and growth factors in a biological sample obtained from an MM patient to provide a peripheral immune profile; and obtaining a level or status of MRD in the MM patient from the peripheral immune profile, wherein if the peripheral immune profile exceeds a pre-determined threshold, the MM patient is positive for MRD.