Monitoring multiple myeloma by next-generation sequencing of V(D)J rearrangements from circulating myeloma cells and cell-free myeloma DNA

TY - JOUR

T1 - Monitoring multiple myeloma by next-generation sequencing of V(D)J rearrangements from circulating myeloma cells and cell-free myeloma DNA

AU - Oberle, Anna

AU - Brandt, Anna

AU - Voigtländer, Minna

AU - Thiele, Benjamin

AU - Radloff, Janina

AU - Schulenkorf, Anita

AU - Alawi, Malik

AU - Akyüz, Nuray

AU - März, Manuela

AU - Ford, Christopher T

AU - Krohn-Grimberghe, Artus

AU - Binder, Mascha

N1 - Copyright © 2017, Ferrata Storti Foundation.

PY - 2017/6

Y1 - 2017/6

N2 - Recent studies suggest that circulating tumor cells and cell-free DNA may represent powerful non-invasive tools for disease monitoring in patients with solid and hematological malignancies. Here, we conducted a pilot study in 27 myeloma patients to explore the clonotypic V(D)J rearrangement for monitoring of circulating myeloma cells (cmc-V(D)J) and cell-free myeloma DNA (cfm-V(D)J). Next-generation sequencing was used to define the myeloma V(D)J rearrangement and for subsequent peripheral blood tracking after treatment initiation. Positivity for cmc-/cfm-V(D)J was associated with conventional remission status (p<0.001) and 91% of non-responders/progressors versus 41% of responders had evidence of persistent cmc-/cfm-V(D)J (p<0.001). About half of the partial responders showed complete clearance of cmc-/cfm-V(D)J 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 cmc- and cfm-V(D)J was associated with each other (p=0.042), but in 30% discordant. This indicated that cfm-V(D)J 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.

AB - Recent studies suggest that circulating tumor cells and cell-free DNA may represent powerful non-invasive tools for disease monitoring in patients with solid and hematological malignancies. Here, we conducted a pilot study in 27 myeloma patients to explore the clonotypic V(D)J rearrangement for monitoring of circulating myeloma cells (cmc-V(D)J) and cell-free myeloma DNA (cfm-V(D)J). Next-generation sequencing was used to define the myeloma V(D)J rearrangement and for subsequent peripheral blood tracking after treatment initiation. Positivity for cmc-/cfm-V(D)J was associated with conventional remission status (p<0.001) and 91% of non-responders/progressors versus 41% of responders had evidence of persistent cmc-/cfm-V(D)J (p<0.001). About half of the partial responders showed complete clearance of cmc-/cfm-V(D)J 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 cmc- and cfm-V(D)J was associated with each other (p=0.042), but in 30% discordant. This indicated that cfm-V(D)J 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.

U2 - 10.3324/haematol.2016.161414

DO - 10.3324/haematol.2016.161414

M3 - SCORING: Journal article

C2 - 28183851

VL - 102

SP - 1105

EP - 1111

JO - HAEMATOLOGICA

JF - HAEMATOLOGICA

SN - 0390-6078

IS - 6

ER -