Routine Evaluation of Minimal Residual Disease in Myeloma Using Next-Generation Sequencing Clonality Testing: Feasibility, Challenges, and Direct Comparison with High-Sensitivity Flow Cytometry

Caleb Ho, Mustafa Syed, Mikhail Roshal, Kseniya Petrova-Drus, Christine Moung, Jinjuan Yao, Andres E. Quesada, Jamal Benhamida, Chad Vanderbilt, Ying Liu, Menglei Zhu, Wayne Yu, Lidia Maciag, Meiyi Wang, Yuanyuan Ma, Qi Gao, Even H. Rustad, Malin Hultcrantz, Benjamin T. Diamond, Binbin Zheng-LinYing Huang, Kasey Hutt, Jeffrey E. Miller, Ahmet Dogan, Khedoudja Nafa, Ola Landgren, Maria E. Arcila

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

The 2016 International Myeloma Working Group consensus recommendations emphasize high-sensitivity methods for minimal residual disease (MRD) detection, treatment response assessment, and prognostication. Next-generation sequencing (NGS) of IGH gene rearrangements is highly specific and sensitive, but its description in routine clinical practice and performance comparison with high-sensitivity flow cytometry (hsFC) remain limited. In this large, single-institution study including 438 samples from 251 patients, the use of NGS targeting the IGH and IGK genes for clonal characterization and monitoring, with comparison to hsFC, is described. The index clone characterization success rate was 93.6% (235/251), which depended on plasma cell (PC) cellularity, reaching 98% when PC ≥10% and below 80% when PC <5%. A total of 85% of cases were successfully characterized using leader and FR1 primer sets, and most clones showed high somatic hypermutation rates (median, 8.1%). Among monitoring samples from 124 patients, 78.6% (147/187) had detectable disease by NGS. Concordance with hsFC was 92.9% (170/183). Discordant cases encompassed 8 of 124 hsFC MRD+/NGS MRD− patients (6.5%) and 4 of 124 hsFC MRD−/NGS MRD+ patients (3.2%), all with low-level disease near detection limits for both assays. Among concordant hsFC MRD−/NGS MRD− cases, only 5 of 24 patients (20.8%) showed subsequent overt relapse at 3-year follow-up. HsFC and NGS showed similar operational sensitivity, and the choice of test may depend on practical, rather than test performance, considerations.

Original languageEnglish (US)
Pages (from-to)181-199
Number of pages19
JournalJournal of Molecular Diagnostics
Volume23
Issue number2
DOIs
StatePublished - Feb 2021
Externally publishedYes

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Medicine

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