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ctDNA Alone Not a Useful Biomarker of Multiple Myeloma Disease Status, Study Says

David Bai, PharmD
There is a lack in correlation between circulating tumor DNA (ctDNA) and bone marrow for minimal residual disease (MRD) by next generation sequencing (NGS) using immunoglobulin genes in patients with multiple myeloma, according to results of a recent study.
There is a lack in correlation between circulating tumor DNA (ctDNA) and bone marrow for minimal residual disease (MRD) by next generation sequencing (NGS) using immunoglobulin genes in patients with multiple myeloma, according to results of a recent study.

Throughout the years, advances in multiple myeloma treatment have greatly improved survival, extending survival from 3 years up to 10 years for patients who are eligible for stem cell transplantations. Better treatments not only increased survival but also improved response rates. With higher response rates comes a need to improve methods to define response to treatment.

MRD in bone marrow through NGS is a highly predictive biomarker that has been used to anticipate survival outcomes in multiple myeloma. Although MRD in bone marrow is very sensitive, it requires repetitive bone marrow aspirations that could be uncomfortable for the patient. ctDNA, also referred to as liquid biopsy, is a new tool that has been developed to monitor treatment through the plasma. If ctDNA has comparable results as bone marrow, it can serve as a convenient replacement strategy in determining MRD as a noninvasive approach. In this study, investigators conducted a prospective study to ascertain whether plasma could replace bone marrow in MRD assessment.

Among the 37 patients with multiple myeloma, there was 49% concordance between paired plasma and bone marrow. The most frequently observed discrepancy was an undetectable MRD in the plasma and a positive MRD in the bone marrow. Negative and positive predictive values with MRD assessment of ctDNA were 36% and 89%, respectively. In addition, investigators found no quantitative correlation between plasma and bone marrow, both when MRD was positive and negative.      

Previously, remission rates were evaluated through indirect immunobiochemical markers such as monoclonal proteins. However, MRD has become increasingly recognized as an assessment tool with remarkably high sensitivity. Even when measuring MRD, there is a significant difference between survival in patients achieving positive MRD (10-5) and MRD negative (<10-6). Because ctDNA was undetectable in 69% of patients with detectable MRD in the bone marrow, ctDNA alone may not be a suitable tool for monitoring MRD until improvements in its applicability are made.

Reference

Mazzotti C, Buisson L, Maheo S, et al. Myeloma MRD by deep sequencing from circulating tumor DNA does not correlate with results obtained in the bone marrow. Blood Adv. 2018;2(21):2811-2813. doi: 10.1182/bloodadvances.2018025197.

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