Evaluation of next-generation sequencing versus next-generation flow cytometry for minimal-residual-disease detection in Chinese patients with multiple myeloma

Mo Zhou; Yan Chen; Yanlei Gong; Mingqing Zhu; Jiannong Cen; Jinlan Pan; Lingzhi Yan; Jingjing Shang; Song Jin; Xiaolan Shi; Weiqin Yao; Shuang Yan; Depei Wu; Suning Chen; Chengcheng Fu; Li Yao

doi:10.1007/s12672-024-00938-w

Evaluation of next-generation sequencing versus next-generation flow cytometry for minimal-residual-disease detection in Chinese patients with multiple myeloma

Discov Oncol. 2024 Mar 19;15(1):78. doi: 10.1007/s12672-024-00938-w.

Authors

Mo Zhou^#^{1

2}, Yan Chen^#¹, Yanlei Gong¹, Mingqing Zhu¹, Jiannong Cen¹, Jinlan Pan¹, Lingzhi Yan¹, Jingjing Shang¹, Song Jin¹, Xiaolan Shi¹, Weiqin Yao¹, Shuang Yan¹, Depei Wu^{1

3}, Suning Chen^{1

3}, Chengcheng Fu¹, Li Yao⁴

Affiliations

¹ National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Soochow University, 188 Shizi Street, Suzhou, 215006, People's Republic of China.
² Hematology Department, Yancheng Third People's Hospital, Yancheng, People's Republic of China.
³ Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, People's Republic of China.
⁴ National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Soochow University, 188 Shizi Street, Suzhou, 215006, People's Republic of China. yaoli78@163.com.

^# Contributed equally.

Abstract

Purpose: To evaluate the efficacy of next-generation sequencing (NGS) in minimal-residual-disease (MRD) monitoring in Chinese patients with multiple myeloma (MM).

Methods: This study analyzed 60 Chinese MM patients. During MRD monitoring in these patients' post-therapy, clonal immunoglobulin heavy chain (IGH) rearrangements were detected via NGS using LymphoTrack assays. MRD monitoring was performed using NGS or next-generation flow cytometry (NGF), and the results were compared. Additionally, the sensitivity and reproducibility of the NGS method were assessed.

Results: The MRD detection range of the NGS method was 10^-6-10^-1, which suggested good linearity, with a Pearson correlation coefficient of 0.985 and a limit of detection of 10^-6. Intra- and inter-assay reproducibility analyses showed that NGS exhibited 100% reproducibility with low variability in clonal cells. At diagnosis, unique clones were found in 42 patients (70.0%) with clonal IGH rearrangements, which were used as clonality markers for MRD monitoring post-therapy. Comparison of NGS and NGF for MRD monitoring showed 79.1% concordance. No samples that tested MRD-positive via NGF were found negative via NGS, indicating the higher sensitivity of NGS. MRD could be detected using NGS in 6 of 7 samples before autologous hematopoietic stem-cell transplantation, and 5 of them tested negative post-transplantation. In contrast, the NGF method could detect MRD in only 1 sample pre-transplantation.

Conclusion: Compared with NGF, NGS exhibits higher sensitivity and reproducibility in MRD detection and can be an effective strategy for MRD monitoring in Chinese MM patients.

Keywords: IGH gene rearrangement; Minimal residual disease; Multiple myeloma; Next-generation flow cytometry; Next-generation sequencing.

Abstract

Grants and funding