Minimal Residual Disease (MRD) Assessment in Multiple Myeloma Patients

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Background

Multiple myeloma (MM) is a neoplastic plasma cell disorder characterized by the proliferation of clonal plasma cells. The introduction of novel drugs and new therapeutic options has led to significantly higher complete response rates and prolonged progression-free survival. Despite these advances, MM remains an incurable disease. Thus, there is a need to refine response criteria and methods more sensitive to evaluate the persistence of lower levels of minimal residual disease. The International Myeloma Working Group has defined the criteria of responses for patients with MM by including MRD. Moreover, depth response based MRD has emerged as one of the most important independent prognostic factors in MM and has been tested as a dynamic tool for monitoring, prognosis, and potential therapeutic endpoint in clinical trials and drugs approvals in MM patients. 
Continuous MRD monitoring based on bone marrow (BM) analysis remains challenging because BM aspiration is an invasive procedure that cannot be repeated frequently. BM-based assays do not allow for the detection of extramedullary disease, which is increasingly seen in the clinic. From this moment on, MRD monitoring during treatment and particularly after therapy currently relies mainly on other less-invasive (but less sensitive) techniques, such as serum-based assessment. Therefore, MRD assays based on peripheral blood (PB) would be worthwhile. Mass spectrometry techniques have recently been used to detect M-protein in serum with more sensitivity than the current electrophoretic methods. 
Other advantages are that it can be used to routinely monitor MM patients after therapy due to its relatively low cost, high throughput, and improved analytical sensitivity and specificity. The new therapeutic protocols for MM distinctly affect the immune cell compartment and the average cell population's regeneration pattern. Also, protocols for MM frequently include continuous treatment to achieve and maintain the depth quality of response. However, this might also result in a cumulative (immunosuppressive) effect on the immune cell with an increased risk of immune deficiency and its complications. 

We welcome Original Research and Review Articles on:
1. Monitoring of minimal residual disease in multiple myeloma by next generation sequencing: the Euroclonality approach 
2. Molecular monitoring of MRD by molecular approaches: perspective on the advantages and limitations of NGS vs ASOqPCR. 
3. Deep genomic characterization of residual tumor plasma cells at the MRD level. 
4. Advantages and limitations of monitoring of CTPC in blood vs bone marrow MRD in multiple myeloma. 
5. Mass-spectrometry for MRD monitoring of M-component light chain in multiple myeloma. 
6. Simultaneous monitoring of MRD and CAR-BCMA T cell therapy in blood of multiple myeloma. 
7. Clinical impact of BM MRD in Amyloidosis - AL 
8. MRD Assessment and Clinical Trials
9. How to apply MRD Assessment in Clinical Practice?



Please note: Manuscripts consisting solely of bioinformatics, computational analysis, or predictions of public databases which are not accompanied by validation (independent cohort or biological validation in vitro or in vivo) will not be accepted in any of the sections of Frontiers in Oncology.

Keywords: Hematologic malignancies, Monoclonal Gammopathies, Multiple Myeloma, Response Criteria, Minimal Residual Disease

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