Table 1.

Drugs, mechanisms of action, involved cytokines and related clinical studies.

Drugs	Mechanism of Action	Cytokines Involved	Resistance	References
Proteasome inhibitors (Bortezomib, carfilzomib ixazomib)	Blockade of NF-kB; interferes with growth arrest, apoptosis, cell cycle progression, inflammation and immune surveillance	Inhibits adhesion of MM cells to BMSCs; reduced production of VEGF-2, FGF-2,IL-6, IGF-I, Ang-1 and Ang-2	Interaction between cytokine-cytokine receptors; autophagy	Zheng et al., 2017 [94] Furukawa Y et al., 2016 [95]
IMIDs(Thalidomide, Lenalidomide pomalidomide)	Selectively enhance degradation of the transcription factors IKZF1 and IKFZ3; anti-angiogenic properties	Modulate TNF-α;reduction of FGF-2,VEGF, IL-6 by MM cells and BMSCs;reduce adhesion between MM PCs and BMSC	Downregulation of cerebron expression	Kortum et al., 2016 [96]
Monoclonal antibodies (elotuzumab, daratumumab, isatuximab)	Antibody-dependent cellular cytotoxicity (ADCC), complement activation, antibody-dependent phagocytosis, direct effect on target cells	Effects mediated by INFγ and TNFα	CDC mechanism mediated by the overexpression of CD55 and CD59	Bellone et al., 2012 [97]
Anti-BCMA BITE CAR	ADC inducing cytotoxic cell death Simultaneous binding to T cell and tumor antigens Chimeric antigen receptors against specific tumor-associated antigen	IL-6, IL-10, TNFα inducing a (CRS)	immunosuppressive TME, production IL-2 by Treg MSC protection	Kankeu Fonkoua et al., 2022 [98]
CELmoDs	rapid degradation of distinct cell types mediated by physical interactions with the CRBN/DDB1 complex	IL-2 up-regulation		Thakurta et al., 2021 [99]