Immune mechanisms contributing to LTS in patients with MM. CD8⁺ and CD4⁺ T cells exhibit increased activation (↑CD57, CD45RA, OX-40) and produce IFN-γ, enhancing antimyeloma responses. NK cells, activated by IL-15 and ADCC, secrete CCL3, CCL4, and CCL5 to target myeloma cells. Naïve and memory B cells increase, whereas regulatory immune cells (MDSCs, TAMs, Tregs, and Bregs) show reduced suppressive activity (reduced IL-10 and PD-1 expression). Reducing the immunosuppressive environment and promoting immune restoration contribute to prolonged tumor growth control. ADCC, antibody-dependent cellular cytotoxicity; Bregs, regulatory B cells; MDSC, myeloid-derived suppressor cell; TAMs, tumor-associated macrophages.