Toward Precision Medicine for Patients with Multiple Myeloma

Abstract

Multiple myeloma (MM), the second most common hematologic malignancy, is a plasma cell neoplasm that arises from a precursor, monoclonal gammopathy of undetermined significance (MGUS), which may or may not be previously diagnosed. Smoldering multiple myeloma (SMM), another precursor of MM, lacks myeloma-defining events and end-organ damage that are diagnostic of MM in the appropriate clinical settings. Newly diagnosed MM (NDMM) is highly heterogeneous genetically and clinically with very variable survival outcomes ranging from a few months to over a decade. Despite this heterogeneity, treatment outcomes have improved significantly in the last two decades, with overall survival improving continuously due to novel classes of drugs approved for treating MM. However, due to the immense heterogeneity, the quest for a cure will almost certainly require individualized patient evaluation and management at every level for every factor influencing patient quality of life and survival, including most importantly determining upfront the progression risks in the precursor states and prognostic risks for progression or relapse in NDMM. Toward that goal, this paper briefly describes, including a historical perspective, current concepts, and recent advances in NDMM for students, researchers, and clinical practitioners. The topics discussed include an overview of the epidemiology, current diagnostic criteria, including for distinguishing MGUS, SMM, and MM, refractory and relapsed MM, staging and prognosis of MM, treatment response criteria, including measurable residual disease evaluation, improvements in survival, current standards for treating NDMM, and disparities and inequities in receiving care in ethnic minority populations for treatment of MM, followed by progress in evaluating the risk of progression in MGUS and SMM, and finally, the genomics of MM, SMM, and MGUS since integrating disease biology in assessing and precisely managing all risk factors and achieving equity in treating all patients would help to achieve that precision medicine goal for a cure.