Cell-free DNA for Genomic Profiling and Minimal Residual Disease Monitoring in Myeloma- Are We There Yet?

Objective: Multiple myeloma (MM), a plasma cell neoplasm, afflicts elder individuals accounting for 10% of hematologic malignancies. The MM plasma cells largely reside within the bone marrow niche and are accessible through an invasive bone marrow biopsy, which is challenging during serial monitoring of patients. In this setting, cell free DNA (cfDNA) may have a role to ascertain the molecular aberrations at diagnosis and in assessment of residual disease during therapy. The aim of this review was to explore the utility and current status of cfDNA in MM.

Method: PubMed was searched with terms including cell-free DNA, circulating-tumor DNA, Multiple Myeloma, diagnosis, genomic profiling, Minimal Residual Disease individually or in combination to shortlist the relevant studies.

Result: cfDNA serves as a non-invasive source of tumor-specific molecular biomarker, ctDNA that has immense potential in facilitating management of cancer patients. The mutation detection platforms for ctDNA include hybrid capture and ultra-deep sequencing. Hybrid capture allows full length gene sequencing for mutation and CNV detection. The disease progression can be monitored by profiling prognostic somatic copy number alterations by ultra-low pass whole genome sequencing of ctDNA cost-effectively. Evolution of both the laboratory protocols and bioinformatics tools may further improve the sensitivity of ctDNA detection for better disease management. Only a limited number of studies were available in MM exploring the potential utility of cfDNA.

Conclusion: In this review, we discuss the nuances and challenges associated with molecular evaluation of cfDNA and its potential role in diagnosis and monitoring of treatment response in MM.