Deep Sequencing Reveals Myeloma Cells in Peripheral Blood in Majority of Multiple Myeloma Patients

作者：Vij Ravi; Mazumder Amitabha; Klinger Mark; O'Dea Denise; Paasch Jacob; Martin Thomas; Weng Li; Park Jeesun; Fiala Mark; Faham Malek; Wolf Jeffrey^*

来源：Clinical Lymphoma Myeloma & Leukemia, 2014, 14(2): 131-139.

DOI：10.1016/j.dml.2013.09.013

• Circulating myeloma clones
• High-throughput sequencing
• Immunoglobulin gene rearrangement
• Minimal residual disease
• Multiple myeloma

A deep-sequencing approach was used to detect and quantify myeloma cells in the peripheral blood in the vast majority of multiple myeloma patients. This study highlights the promise of a blood-based, sequencing assay for minimal residual disease that can be used to measure multiple myeloma disease burden at different time points and various disease stages.
Introduction: The evaluation of myeloma cells in multiple myeloma (MM) patients has generally been limited to the assessment of bone marrow involvement because of the sensitivity limitations of traditional minimal-residual-disease detection methods. Materials and Methods: We developed a sequencing-based method to identify nnyeloma cells in bone marrow (BM) and peripheral blood (PB) samples, based on their unique immunoglobulin gene rearrangements, that can detect cancer clones at levels well below 1 in 1 million leukocytes (0.0001%). In this multisite study, we used this sequencing method to determine the fraction of patients with myeloma cells in their PB at diagnosis and post-treatment time points. Results: Using this sequencing approach, we detected myeloma cells in the PB in the vast majority of MM patients (44/46, 96%). We demonstrated a clear correlation (R-2 = 0.57) between myeloma clone levels in paired BM and PB samples, and noted that PB clone levels were approximately 100-fold lower than levels in BM samples. The sequencing assay demonstrated a clear sensitivity advantage in the BM compartment and at least equivalent sensitivity in the PB compared with that of monoclonal-protein results. Conclusion: This study highlights the promise of a blood-based, sequencing minimal-residual-disease assay that can be used to measure MM disease burden at different time points and various disease stages.

• 出版日期2014-4