Standardized minimal residual disease detection by next generation sequencing in multiple myeloma

2019 ◽  
Vol 19 (10) ◽  
pp. e175
Author(s):  
Qiumei Yao ◽  
Yinlei Bai ◽  
Alberto Orfao ◽  
James Chim
Keyword(s):  
Multiple Myeloma ◽  
Next Generation Sequencing ◽  
Minimal Residual Disease ◽  
Residual Disease ◽  
Disease Detection ◽  
Next Generation ◽  
Minimal Residual Disease Detection ◽  
Generation Sequencing ◽  
Minimal Residual

A comparison between next-generation sequencing and ASO-qPCR for minimal residual disease detection in multiple myeloma.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8601-8601
Author(s):  
Hiroyuki Takamatsu ◽  
Ryoichi Murata ◽  
Jianbiao Zheng ◽  
Martin Moorhead ◽  
Yasushi Terasaki ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Next Generation Sequencing ◽  
Minimal Residual Disease ◽  
Residual Disease ◽  
Survival Rates ◽  
Japanese Patients ◽  
Next Generation ◽  
Universal Primer ◽  
Generation Sequencing ◽  
Minimal Residual

8601 Background: Although molecular CR in multiple myeloma (MM) can be assessed by allele-specific oligonucleotide (ASO)-PCR, this technique requires preparation of clonotype-specific primers for each individual which is laborious and time-consuming. The usage of the LymphoSIGHT method, a next-generation sequencing (NGS)-based platform, may overcome these challenges and increase sensitivity and specificity. We compared the LymphoSIGHT approach with ASO-qPCR for minimal residual disease (MRD) detection in autografts in the autologous peripheral blood stem cell transplantation (ASCT) setting. Methods: Seventeen Japanese patients with newly diagnosed MM who received various induction regimens prior to ASCT were retrospectively analyzed. All patients had achieved a PR or CR after ASCT. Bone marrow (BM) slides from 13 MM patients and fresh BM cells from 4 MM patients at diagnosis as well as autografts were obtained for DNA extraction. Using universal primer sets, we amplified IGH variable (V), diversity (D), and joining (J) gene segments, IGH-DJ, and IGK from genomic DNA. Amplified products were subjected to deep sequencing using NGS. Reads were analyzed using standardized algorithms for clonotype determination. Myeloma-specific clonotypes were identified for each patient based on their high frequency in BM samples. The presence of the myeloma clonotype was then assessed in follow-up samples. Results: MRD in autografts was detected in 6 of 17 (35%) by ASO-qPCR and 13 of 17 (76%) by NGS. When MRD was assessed by NGS, 6 MRD (+) cases received post-ASCT therapy while 4 MRD (-) cases and 7 MRD (+) cases were followed without post-ASCT therapy. The MRD (-) cases tended to show a better PFS than the MRD (+) cases with post-ASCT therapy (P = 0.26) and those without post-ASCT therapy (P = 0.09) although overall survival rates were comparable among the three groups. There was no difference in PFS between MRD (-) and MRD (+) cases when MRD was assessed by ASO-qPCR (P = 0.6). These studies will be extended in 30 additional MM patients, and results will be presented. Conclusions: MRD-negativity in autografts revealed by NGS may be more closely associated with durable remission of MM than that revealed by ASO-qPCR.

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