Abstract

Multiple Myeloma (MM), the second most common hematologic malignancy, has been the target of many therapeutic advances over the past two decades. The introduction of novel agents, such as proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies, along with autologous hematopoietic stem cell transplantation (ASCT) in the current standard of care, has increased the median survival of myeloma patients significantly. Nevertheless, a curative treatment option continues to elude us, and MM remains an incurable disease, with patients relapsing even after achieving deep conventionally defined responses, underscoring the need for the development of sensitive methods that will allow for proper identification and management of the patients with a higher probability of relapse. Accurate detection of Minimal Residual Disease (MRD) from a bone marrow biopsy represents a relatively new approach of evaluating response to treatment with data showing clear benefit from obtaining MRD(-) status at any point of the disease course. As life expectancy for patients with MM continues to increase and deep responses are starting to become the norm, establishing and refining the role of MRD in the disease course is more relevant than ever. This review examines the different methods used to detect MRD and discusses future considerations regarding the implementation in day-to-day clinical practice and as a prospective primary endpoint for clinical trials.

Highlights

  • In recent years, with the advent of new therapeutic regimens and monoclonal antibodies, the landscape of treatment options for Multiple Myeloma (MM) has substantially changed, leading to significantly increased complete response (CR) rates and prolonged survival [1, 2]

  • Proportion of participants who reach MRD negativity upfront or after consolidation Overall Response Rate (ORR) MRD negativity. This phase 2 trial will test whether the combination of DaraRd as induction therapy, followed by DRVd consolidation therapy, if needed, will result in more patients achieving minimal residual disease MRD negative status, relative to the standard of care

  • After induction therapy with KRdD (Kyprolis, Revlimid, dexamethasone, negativity at Darzalex), duration of consolidation and maintenance therapy will be the guided by MRD rates

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Summary

Charalampos Charalampous and Taxiarchis Kourelis*

Specialty section: This article was submitted to Hematologic Malignancies, a section of the journal Frontiers in Oncology. Multiple Myeloma (MM), the second most common hematologic malignancy, has been the target of many therapeutic advances over the past two decades. A curative treatment option continues to elude us, and MM remains an incurable disease, with patients relapsing even after achieving deep conventionally defined responses, underscoring the need for the development of sensitive methods that will allow for proper identification and management of the patients with a higher probability of relapse. As life expectancy for patients with MM continues to increase and deep responses are starting to become the norm, establishing and refining the role of MRD in the disease course is more relevant than ever. This review examines the different methods used to detect MRD and discusses future considerations regarding the implementation in day-to-day clinical practice and as a prospective primary endpoint for clinical trials

INTRODUCTION
BONE MARROW ASSESSMENT METHODS
Euroflow MFC antibodies
Turnaround for results Availability
ASSOCIATION BETWEEN MRD NEGATIVE STATUS AND PROGNOSIS
BARRIERS IN INCORPORATING MRD TESTING IN CLINICAL PRACTICE
Brief outline
Overall Survival
Full Text
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