Emerging Monoclonal Antibodies for the Treatment of Multiple Myeloma

Abstract

Therapeutic measures designed to treat multiple myeloma (MM) have undergone a fundamental shift over the past two decades as a number of small molecules that attack this cancer by different mechanisms, including proteasome blockade, immunomodulation, and histone deacetylase (HDAC) inhibition, have been introduced. The insertion of monoclonal antibodies (mAbs) into the mix began in 2015 with the U.S. Food and Drug Administration (FDA) approval of daratumumab and elotuzumab, which target CD38 and SLAMF7, respectively. In 2020, they were joined by another anti-CD38 mAb, isatuximab, and the bispecific antibody-drug conjugate (ADC) belantamab mafodotin, which targets the B-cell maturation antigen (BCMA). This review focuses on additional mAbs currently under clinical study for MM. These include several BCMAxCD3-directed bispecifics (AMG 420, AMG 701, REGN5458, REGN5459, teclistamab, and TNB-383B), the ADCs indatuximab ravtansine and STRO-001, and checkpoint inhibitors, although the future status of the latter is in a state of flux due to toxicity issues that arose in trials in which these drugs, especially PD-1 or PD-L1 blockers, were combined with immunomodulators.

Current Status of Novel Agents for the Treatment of B Cell Malignancies: What’s Coming Next?

“…Along with daratumumab and isatuximab, several novel CD38-targeting strategies are being developed (mostly for MM); these include the use of naked anti-CD38 mAbs, anti-CD38 ADCs, anti-CD38/CD3 BiTEs, and CD38-targeting CAR-T cells [ 195 , 247 , 251 , 258 ]. Felzartamab (MOR202; TJ202) and TAK-079 are both fully human IgG1 mAbs [ 251 , 259 ]. Although felzartamab showed promising efficacy in MM (both alone and combined with immunomodulators; NCT01421186) [ 260 ], the drug’s sponsor (MorphoSys AG) unexpectedly stopped this development in 2020 [ 259 ].…”

“…Felzartamab (MOR202; TJ202) and TAK-079 are both fully human IgG1 mAbs [ 251 , 259 ]. Although felzartamab showed promising efficacy in MM (both alone and combined with immunomodulators; NCT01421186) [ 260 ], the drug’s sponsor (MorphoSys AG) unexpectedly stopped this development in 2020 [ 259 ]. However, two ongoing trials are evaluating the effect of a combination of felzartamab and conventional therapies in patients with R/R MM ( Table 3 ).…”