Dr. Richardson on Treatment Approaches Targeting Mutational Burden in Myeloma

Paul G. Richardson, MD, clinical program leader, director of clinical research, Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, and RJ Corman Professor of Medicine, Harvard Medical School, discusses treatment approaches targeting mutational burden in multiple myeloma.

Targeting mutational burden is very important in myeloma, says Richardson. One of the agents that has shown particular promise in doing so is venetoclax (Venclexta), specifically in patients with (11;14) translocations. Recently, venetoclax was flagged for safety concerns in a clinical trial that evaluated the agent in combination with bortezomib (Velcade) and dexamethasone. If the FDA warning is cleared, Richardson is confident that the clinical benefit seen with the agent among patients with t(11;14) will warrant further exploration.

Additionally, there are several novel small molecules under evaluation. One of the most exciting agents is the selective inhibitor of nuclear export small molecule, selinexor, says Richardson. It is an oral agent that is given once or twice a week. When administered once weekly in combination it appears to be very active, particularly in combination with other drugs such as bortezomib, says Richardson.

The drug operates by blocking the export of proteins that would normally suppress the malignant genome, and therein the oncogenic thrust, explains Richardson. In doing so, it allows for stabilization of the malignant genome in a way that is proapoptotic and triggers a control of the malignant cell. This will likely be very valuable to patients—especially those with high-risk disease. Although the FDA voted against an accelerated approval of the agent, subsequently extending its review period, it is likely to be approved sometime this year, predicts Richardson.