Table 2.

Some target inhibitors, antagonists, or antibodies in multiple myeloma

Targets	Modulators	Function	Investigational stage	Results	Reference
CXCL12-CXCR4	Olaptesed pegol (NOX-A12)	CXCL12 (SDF-1) inhibitor Inhibiting dissemination and colonization of MM cells	Phase II	Confirmed safety and efficacy at least 72 h	[57, 86]
	F50067	CXCR4 antagonist Sensitizing MM cells to LEN and dexamethasone Inducing CDC and ADCC	Phase I	Observed dose-limiting toxicity	[87]
	Plerixafor (AMD3100)	CXCR4 antagonist Sensitizing MM cells to bortezomib Mobilizing hematopoietic cells	Phase II	Confirmed safety and efficacy in combination with bortezomib in MM	[6]
			Phase IV	Confirmed safety and efficacy in improving mobilization of aHSCs.	[8]
	Ulocuplumab	CXCR4 monoclonal antibody Improving overall response rate to standard therapy	Phase II	Confirmed safety and efficacy in combination with either LEN and dexamethasone or bortezomib and dexamethasone in MM	[7]
	Motixafortide (BKT140)	CXCR4 antagonist Mobilizing hematopoietic cells	Phase III	Confirmed safety and efficacy of mobilization in MM	[9]
IL-6	Siltuximab (CNTO 328)	IL-6 monoclonal antibody Inhibiting smoldering MM from transiting to MM	Phase II	Confirmed safety and failure to meet the desired effect	[70]
VEGF	Zactima (ZD6474)	VEGFR and EGFR inhibitor Inhibiting angiogenesis	Phase II	Confirmed safety while no reduction of M protein	[71]
	Sorafenib (BAY 43-9006)	Raf-kinase and VEGFR inhibitor Inhibiting Raf-signaling pathway and angiogenesis	Phase II	No activity by the International Uniform Response Criteria for MM	[72]
	Bevacizumab	VEGF-A monoclonal antibody Inhibiting angiogenesis	Phase II	No significant difference between combination therapy and single-agent thalidomide or single-agent bortezomib	[73, 74]
	Semaxinib (SU5416)	RTKI of VEGFR-2 Inhibiting VEGF-induced angiogenesis	Phase II	Minimal clinical activity	[75]
	Pazopanib	VEGFR, PDGFR, and c-Kit inhibitor Inhibiting angiogenesis	Phase II	No meaningful clinical responses in the single-agent treatment	[76]
CD38 (Only post-phase III modulators are listed.)	Daratumumab	CD38 monoclonal antibody Sensitizing MM cells to proteasome inhibitors	Phase IV	Confirmed benefits in combination with carfilzomib and dexamethasone	[78]
	Isatuximab	CD38 monoclonal antibody Inducing MM cells’ apoptosis	Phase IV	Confirmed benefits in combination with carfilzomib and dexamethasone	[79]
SLAMF7	Elotuzumab	SLAMF7 monoclonal antibody Inducing ADCC, ADPC and inhibiting adhesion of MM cells	Phase IV	Confirmed benefits in combination with LEN and dexamethasone	[80–82]
BCMA (Only post-phase III modulators are listed.)	Teclistamab	BCMA and CD3 bispecific antibody Inducing T cells’ activation and MM cells’ apoptosis	Phase IV	Approved treatments in relapsed or refractory MM	[83]
	Belantamab mafodotin	ADC targeting BCMA Inducing MM cells’ apoptosis and activation of anti-tumor immune responses	Phase IV	Approved treatments in pluri-refractory patients	[85]
	Elranatamab	BCMA and CD3 bispecific antibody Inducing T-cell mediated cytotoxicity	Phase IV	Observed promising early responses with manageable safety	[84]
GPRC5D	Talquetamab	CD3 and GPRC5D bispecific antibody Mediating immune cells to attack GPRC5D-expressing MM cells	Phase III	Confirmed response and safety in treating relapsed or refractory MM in phase II trial	[77]

Abbreviations: SDF-1 Stromal Cell-derived Factor-1, MM Multiple myeloma, LEN Lenalidomide, aHSCs Autologous hematopoietic stem cells, CDC Complement-dependent cytotoxicity, ADCC Antibody-dependent cellular cytotoxicity, VEGFR Vascular endothelial growth factor receptor, EGFR Endothelial growth factor receptor, VEGF Vascular endothelial growth factor, RTKI Tyrosine kinase inhibitor, PDGFR Platelet-derived growth factor receptor, SLAMF7 Signaling lymphocytic activation molecule F7, ADPC Antibody-dependent cellular cytotoxicity, BCMA B-cell maturation antigen, ADC Antibody-drug conjugate, GPRC5D G protein-coupled receptor class C group 5 member D