Biomarker-directed therapy in multiple myeloma.

PURPOSE OF REVIEW: Multiple myeloma is currently treated with a one-size-fits-all approach despite significant heterogeneity in patient outcomes and disease molecular constitution. A personalised approach would tailor therapy to unique patient or disease characteristics.

RECENT FINDINGS: Well established prognostic biomarkers such as cytogenetic risk and patient frailty status are being evaluated as potential predictive biomarkers. Specifically, treatment intensity can be augmented in high-risk patients or conversely attenuated in those at lower risk or lower ability to withstand treatment toxicities. Alternatively, targeted therapy can be rationally designed to exploit vulnerable pathways in myeloma cells as identified using predictive biomarkers. The t(11;14) translocation, found in approximately 15-20% of myeloma cases, is a leading biomarker for response to BCL-2 inhibitors such as venetoclax.

SUMMARY: Active research efforts exploring venetoclax combination therapies, as well as new generation BCL-2 inhibitors are underway. Following the development of venetoclax, numerous other cellular pathways are under investigation as candidate predictive biomarkers to rationally inform newer targeted therapies in myeloma.