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 72Â h | |
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 | ||
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 | |
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] |