Abstract
The basic principle that deeper therapeutic responses lead to better clinical outcomes in cancer has emerged technologies capable of detecting rare residual tumor cells. The need for ultra-sensitive approaches for minimal residual disease (MRD) detection is particularly evident in Multiple Myeloma (MM), where patients will ultimately relapse despite the achievement of complete remission, which is commonplace due to remarkable therapeutic advances. Consequently, current response criteria on MM have been amended based on MRD status and MRD negativity is now considered the most dominant prognostic factor and the most valuable indicator for a subsequent relapse. However, there are particular limitations and several aspects for MRD assessment that remain open. This review summarizes current data on MRD in the clinical management of MM, highlights open issues and discusses the challenges and the endless opportunities arising for both patients and clinicians. Furthermore, it focuses on the current status of MRD in clinical trials, its dynamics in addressing debatable aspects in the clinical handling and its potential role as the prevailing factor for future MRD-driven tailored therapies.
Highlights
The extended research and coordinated efforts to understand the biology and the clinical aspects of Multiple Myeloma (MM) has currently led to the development of novel regimens, drugs, and therapeutic approaches which offer a clear benefit in favor of the patients
Their results highlighted that the achievement of PET-complete remission (CR) after treatment was correlated with longer progression free survival (PFS: 27, 6 months for PET-negative vs. 18 months for PET positive, P < 0.05) whereas the Maximum standardized uptake value (SUVmax) ≥4,2 after treatment was an independent unfavorable prognostic factor
Results from the IFM/DFCI2009 study have shown that patients with upfront autologous stem cell transplantation (ASCT) after 3 cycles of RVd induction experienced better therapeutic responses than those treated with 8 cycles RVd therapy and delayed ASCT [74]
Summary
The extended research and coordinated efforts to understand the biology and the clinical aspects of Multiple Myeloma (MM) has currently led to the development of novel regimens, drugs, and therapeutic approaches which offer a clear benefit in favor of the patients. The therapeutic efficacy is reflected by the massive increase of the number of patients achieving complete remission (CR), followed by extended periods free of progression. Based on the basic principle that the deeper the remission the better controllable the disease, it is of utmost clinical significance to be able to assess the efficiency-depth of a selected treatment and anticipate an eventual relapse. The presence of Minimal Residual Disease (MRD), i.e., minute numbers of myeloma cells that may remain in the bone marrow (BM) of the patient after treatment, has been proved crucial for monitoring remission status and is regarded as the major cause of relapse. Current technology allows for the detection of MRD at levels as low as one myeloma cell in one million of total examined cells, providing brand new opportunities for both clinicians and patients
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