Treatment strategies for multiple myeloma based on molecular biology and cytogenetic abnormalities

Abstract

Multiple myeloma (MM) is characterized by several cytogenetic abnormalities that occur at various time points during the disease course. Cytogenetic abnormalities in MM cells are critical intrinsic factors that determine tumor characteristics, and reflect sensitivity to key drugs including proteasome inhibitors, immunomodulatory drugs, and anti-CD38 monoclonal antibodies. Venetoclax, a first-in-class BCL-2 inhibitor, is currently under investigation for the treatment of t (11;14) MM. Some cytogenetic abnormalities may also be associated with poor response to BCMA-targeting bispecific antibodies and CAR-T therapy. The biological and clonal heterogeneity of MM complicates treatment stratification according to biology and risk. Consequently, cytogenetic abnormalities play an important role in treatment stratification for this heterogenous disease, and precision medicine based on cytogenetic abnormalities can be expected eventually.