Opportunities and challenges for MRD assessment in the clinical management of multiple myeloma

Abstract

Measurable residual disease (MRD) assessment is, from the methodological point of view, ready for prime time in multiple myeloma (MM). Abundant evidence underscores the value of MRD status determined using highly sensitive next-generation flow cytometry and next-generation sequencing tests in evaluating response to treatment and, therefore, prognosis in patients with this disease. MRD response assessment and monitoring might present a range of opportunities for individualized patient management. Moreover, the considerable amounts of high-quality and standardized MRD data generated in clinical trials have led to the acceptance of MRD negativity as an early end point for accelerated regulatory approval of treatments for MM. The data leave no doubt that the efficacy of new regimens in inducing deeper and durable MRD-negative responses is connected with prolonged survival. Yet, several evidential, technical and practical challenges continue to limit the implementation of MRD-guided treatment strategies in routine practice, and the use of MRD as a surrogate end point remains controversial to some. In this Review, we draw on past and present research to propose opportunities for overcoming some of these challenges, and to accelerate the use of MRD assessment for improved clinical management of patients with MM. Multiple myeloma is a malignancy at the forefront of measurable residual disease (MRD) assessment. In this Review, the authors describe the evolution of MRD analysis in multiple myeloma from technical and clinical standpoints, and discuss opportunities and challenges for MRD-guided management of this disease.