Panobinostat, a pan-histone deacetylase inhibitor: Rationale for and application to treatment of multiple myeloma

Histone deacetylase inhibitors (HDACis) have emerged as novel therapeutic agents for cancer. Currently, four HDACis are approved by the Food and Drug Administration (FDA) to treat various hematologic malignancies. Panobinostat (LBH-589, trade name Farydak®, developed and marketed by Novartis) is a potent pan-HDACi with demonstrated anticancer activities against multiple myeloma, a B-cell malignancy, at a low nanomolar range in preclinical settings, and in 2015 was granted FDA approval for the treatment of relapsed and refractory multiple myeloma. Here, we review the development of HDACis, the unique features of panobinostat, and the rationale for developing panobinostat in a combination setting for the treatment of multiple myeloma. We also review the completed and ongoing clinical trials testing the efficacy of panobinostat in combination therapies and highlight future therapeutically relevant strategies.