Minimal residual disease in myeloma: are we there yet?

Measurement of minimal residual disease is routine in diseases such as chronic myelogenous leukemia, precursor B cell acute lymphoblastic leukemia, and acute promyelocytic leukemia because it provides important prognostic information. However, the role of minimal residual disease testing has not been widely adopted in multiple myeloma (MM), with other parameters such as the International Staging System (ISS) and cytogenetic analysis primarily guiding therapy and determination of prognosis. Until recently, achieving a complete response (CR), as defined by the International Myeloma Working Group (IMWG) criteria, was rare in patients with MM. The use of novel agents with or without autologous peripheral blood stem cell transplantation (auto-PBSCT) has significantly increased CR rates, thus increasing overall survival (OS) rates. The majority of patients with MM have persistent levels of residual disease that are below the sensitivity of bone marrow (BM) morphology, protein electrophoresis with immunofixation, and light chain quantitation even after attaining CR and will eventually relapse. Measurement of minimal residual disease by more sensitive methods, and the use of these methods as a tool for predicting patient outcomes and guiding therapeutic decisions, has thus become more relevant. Methods available for monitoring minimal residual disease in MM include PCR and multiparameter flow cytometry (MFC), both of which have been shown to be valuable in other hematologic malignancies; however, neither has become a standard of care in MM. Here, we review current evidence for using minimal residual disease measurement for risk assessment in MM as well as incorporating pretreatment factors and posttreatment minimal residual disease monitoring as a prognostic tool for therapeutic decisions, and we outline challenges to developing uniform criteria for minimal residual disease monitoring.