Monitoring multiple myeloma by next-generation sequencing of V(D)J rearrangements from circulating myeloma cells and cell-free myeloma DNA.
Recent studies suggest that circulating tumor cells and cell-free DNA may represent powerful non-invasive tools for monitoring disease in patients with solid and hematologic malignancies. Here, we conducted a pilot study in 27 myeloma patients to explore the clonotypic V(D)J rearrangement for monitoring circulating myeloma cells and cell-free myeloma DNA. Next-generation sequencing was used to define the myeloma V(D)J rearrangement and for subsequent peripheral blood tracking after treatment initiation. Positivity for circulating myeloma cells/cell-free myeloma was associated with conventional remission status (P<0.001) and 91% of non-responders/progressorsversus41% of responders had evidence of persistent circulating myeloma cells/cell-free myeloma DNA (P<0.001). About half of the partial responders showed complete clearance of circulating myeloma cells/cell-free myeloma DNA despite persistent M-protein, suggesting that these markers are less inert than the M-protein, rely more on cell turnover and, therefore, decline more rapidly after initiation of effective treatment. Positivity for circulating myeloma cells and for cell-free myeloma DNA were associated with each other (P=0.042), but discordant in 30% of cases. This indicates that cell-free myeloma DNA may not be generated entirely by circulating myeloma cells and may reflect overall tumor burden. Prospective studies need to define the predictive potential of high-sensitivity determination of circulating myeloma cells and DNA in the monitoring of multiple myeloma.
Department of Oncology and Hematology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Anna
A
Oberle
Department of Oncology and Hematology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Anna
A
Brandt
Department of Oncology and Hematology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Minna
M
Voigtlaender
Department of Oncology and Hematology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Benjamin
B
Thiele
Department of Oncology and Hematology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Janina
J
Radloff
Department of Oncology and Hematology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Anita
A
Schulenkorf
Bioinformatics Core, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Malik
M
Alawi
Department of Oncology and Hematology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Nuray
N
Akyüz
Department of Oncology and Hematology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Manuela
M
März
Department of Oncology and Hematology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Christopher T
CT
Ford
LYTIQ GmbH, Paderborn, Germany.|Analytische Informationssysteme und Business Intelligence, Universität Paderborn, Germany.
Artus
A
Krohn-Grimberghe
Department of Oncology and Hematology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany m.binder@uke.de.
Mascha
M
Binder
D000368:Aged; D015415:Biomarkers; D004273:DNA, Neoplasm / Q000032:analysis*; D005260:Female; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000175:diagnosis*; D009360:Neoplastic Cells, Circulating / Q000378:metabolism*; D010865:Pilot Projects; D047368:Tumor Burden; D060152:V(D)J Recombination / Q000235:genetics*
D015415:Biomarkers; D004273:DNA, Neoplasm