Race for the Cure: From the Oldest to the Newest Monoclonal Antibodies for Multiple Myeloma Treatment

Abstract

Multiple myeloma is characterized by a wide clinical heterogeneity due to an intricate network of interactions between bone marrow-resident clonal plasma cells and the microenvironment. Over the last years, dramatic improvement in the understanding of these pathways led to the introduction of novel drugs with immune-mediated mechanisms of action. Some of these compounds, such as the anti-cd38 daratumumab and isatuximab, the anti-slamf-7 elotuzumab, and the antibody-drug conjugate belantamab-mafodotin, have been tested in large clinical trials and have now fully entered the real-life management. The bispecific T-cell engagers are under investigation with promising results, and other satisfactory data is expected from the application of nanotechnologies. The perfect timing to introduce these drugs in the sequence of treatment and their adverse events represent new challenges to be addressed, and further experience is required to improve their use.

Keywords: immune therapy; monoclonal antibodies; multiple myeloma; nanobodies.

Figure 1

Overview of mechanisms of action of mOabs. MMAE: monometyl-auristatin-F; ADCC: antibody-dependent cell-mediated cytotoxicity; ADCP: antibody-dependent cellular phagocytosis; CDC: complement-dependent cytotoxicity.

Figure 2

(a) Comparison of antibody and nanobody structure. In both cases, the yellow line separates the FAB fragments from the FC fragment. CH: constant heavy chain domain; VH: variable heavy chain domain; CL: constant heavy chain domain; VL: variable heavy chain domain. (b) Aptamer structure: single-stranded oligonucleotide with complementary sequence to the target.