New drugs on the horizon. Treatment of myeloma in 2020, a perspective

This minireview covers novel drugs and treatment concepts being evaluated in early studies for therapy of patients with multiple myeloma (MM). Panobinostat, a histone deacetylase inhibitor, showed limited improvement in progression-free survival, thus raising doubt whether these substances will provide clinical meaningful benefits in MM. Some of the new proteasome inhibitors beyond carfilzomib offer the benefit of oral administration and reduced neurotoxicity. Monoclonal antibodies with antimyeloma or antistroma cell activity raise expectations for improved treatment outcome when combined with conventional chemotherapy. A series of new inhibitors of signal pathways important for proliferation and progression in MM presently are scrutinized for their clinical usefulness. Among these, inhibitors of the mitogen activated protein kinase (MAPK), epidermal growth factor receptor (EGFR), protein kinase B (AKT), and B-cell receptor pathway as well as drugs inhibiting the spindle protein, Bcl-2, and cyclin-dependent kinases show promise for becoming important antimyeloma dugs. Checkpoint inhibitors have shown significant activity in some solid tumors and are now tested in MM as well. Measles viruses bind via CD46 to myeloma cells, self-amplify at sites of tumor growth, and induce cell death in myeloma but not in normal cells, thus offering a completely new treatment strategy. However, before introduction of these interesting approaches into the clinic, confirmation of their clinical efficacy is needed.