MRD Testing in Multiple Myeloma: The Main Future Driver for Modern Tailored Treatment

The past decade, several highly efficacious drugs have been approved for the treatment of multiple myeloma. Many of these newer drugs are less toxic than older chemotherapy drugs. Using modern combination therapy in newly diagnosed multiple myeloma patients, high proportions of newly diagnosed multiple myeloma patients obtain minimal residual disease (MRD) negativity and MRD testing has rapidly become an integral part of clinical trials focusing on patients in this setting. Only recently, MRD negativity was reported in clinical trials focusing on older newly diagnosed multiple myeloma patients (ie, nontransplant candidates), as well as studies focusing on patients with relapsed or refractory multiple myeloma. In the past, deeper responses were rarely seen in these patient categories due to inferior therapies and lack of MRD assays. The reason for the rapidly increased interest in MRD testing in all types of clinical trials is the fact that MRD negativity is closely correlated with longer progression-free survival which has been documented in recent meta-analyses. Consequently, MRD negativity has the potential to soon become a regulatory surrogate end-point for drug approval. This review dissects and discusses current data on MRD in multiple myeloma, it outlines new hypotheses, which can be tested in future clinical studies, and it discusses opportunities and future avenues for translational research. The goal of this article is to stimulate critical analysis of our current treatment landscape and development of future translational research involving MRD testing.