New drugs on the horizon. Treatment of myeloma in2020, a perspective

摘要

This minireview covers novel drugs and treat-ment concepts being evaluated in early studies for ther-apy of patients with multiple myeloma (MM). Panobi-nostat, a histone deacetylase inhibitor, showed limitedimprovement in progression-free survival, thus raisingdoubt whether these substances will provide clinicalmeaningful benefits in MM. Some of the newproteasomeinhibitors beyond carfilzomib offer the benefit of oraladministration and reduced neurotoxicity. Monoclonalantibodies with antimyeloma or antistroma cell activityraise expectations for improved treatment outcome whencombined with conventional chemotherapy. A series ofnew inhibitors of signal pathways important for prolif-eration and progression in MM presently are scrutinizedfor their clinical usefulness. Among these, inhibitors ofthe mitogen activated protein kinase (MAPK), epidermalgrowth factor receptor (EGFR), protein kinase B (AKT)and B-cell receptor pathway as well as drugs inhibitingthe spindle protein, Bcl-2 and cyclin-dependent kinasesshow promise for becoming important antimyelomadugs. Checkpoint inhibitors have shown significantactivity in some solid tumors and are now tested in MMas well. Measles viruses bind via CD46 to myeloma cells,self-amplify at sites of tumor growth, and induce celldeath in myeloma but not in normal cells, thus offeringa completely new treatment strategy. However, before introduction of these interesting approaches into theclinic, confirmation of their clinical efficacy is needed.