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Achieving minimal residual disease-negative by multiparameter flow cytometry may ameliorate a poor prognosis in MM patients with high-risk cytogenetics: a retrospective single-center analysis

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Abstract

The aim of our study was to evaluate the prognostic impact of minimal residual disease (MRD) and high-risk cytogenetics (HRCs) on outcomes in multiple myeloma (MM) patients. We applied multiparameter flow cytometry (MFC) to detect MRD in 123 consecutive patients diagnosed with MM for the first time who achieved very good partial remission (VGPR) or better after bortezomib or thalidomide-based induction therapy. Moreover, we examined the cytogenetic features of MM patients using magnetic-activated cell sorting and interphase fluorescence in situ hybridization (MACS-iFISH) at diagnosis. In all 123 MM patients, progression-free survival (PFS) and overall survival (OS) were better in the MRD− group (n = 31) than in the MRD+ group (n = 92) (median PFS: not reached (NR) vs. 26 months (m), P = 0.0002; 4-year OS, 91.7% vs. 66.3%, P = 0.008). PFS and OS were significantly shorter for each increase of one log per MRD level (P < 0.0001 and P = 0.001). The median PFS of the four groups according to the ratio of aberrant plasma cells (less than 0.01%, 0.01–0.1%, 0.1–1%, and more than 1%) were NR, 37 m, 26 m, and 15 m, respectively, and the 4-year OS rates were 91.7%, 69.3%, 76.1%, and 54.0%, respectively. In addition, our results show that PFS and OS were better for the standard-risk cytogenetic (SRC) patients than the HRC patients (median PFS: NR vs. 26 m, P = 0.004; 3-year OS: 95.8% vs. 76.0%, P = 0.006). The independent predictors of PFS were HRC and MRD+, which had hazard ratios of 1.901 (95% CI 1.094–3.303) and 3.486 (95% CI 1.449–8.386), respectively; while those for OS were an LDH level ≥ 250 U/L, HRC, and MRD+, which had hazard ratios of 2.789 (95% CI 1.080–7.199), 2.697 (95% CI 1.053–6.907), and 7.714 (95% CI 1.040–57.227), respectively. Furthermore, for SRC patients or HRC patients, PFS and OS were all longer in MRD− than in MRD+ patients. Strikingly, there was no significant difference in PFS or OS between the MRD-HRC and MRD+SRC groups (median PFS 45 vs. 34 m, P = 0.300; 4-year OS 100% vs. 83.6%, P = 0.196). PFS was superior in MRD-SRC than in MRD-HRC (NR vs. 45 m, P = 0.035); however, there was no significant difference in the 4-year OS between MRD-SRC and MRD-HRC (87.5% vs 100%, P = 0.480). MRD+ and HRCs were both independent prognostic factors in MM patients. Moreover, achieving MRD− may ameliorate a poor prognosis in MM patients with HRCs.

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Abbreviations

MFC:

Multiparameter flow cytometry

BM:

Bone marrow

MRD:

Minimal residual disease

SRC:

Standard-risk cytogenetics

HRCs:

High-risk cytogenetics

HD:

Hyperdiploidy

NHD:

Non-hyperdiploidy

APCs:

Aberrant plasma cells

NPCs:

Normal plasma cells

MACS-iFISH:

Magnetic-activated cell sorting and interphase fluorescence in situ hybridization

CR:

Complete remission

sCR:

Stringent CR

VGPR:

Very good partial remission

Ig:

Immunoglobulin

ISS:

International Staging System

LC:

Light chain

PFS:

Progression-free survival

OS:

Overall survival

NR:

Not reached

IMWG:

International Myeloma Working Group

PCR:

Polymerase chain reaction

NGS:

Next-generation sequencing

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Acknowledgments

We sincerely thank all the doctors and nurses in the hematology department. In particular, we thank our colleagues who participated in this study. We thank all the patients who participated in this study and who sought care at our center.

Funding

This work is supported by projects from the National Natural Science Foundation of China for Young Scholars (grant number 81800126), the Six Talent Peak Project in Jiangsu Province (grant number 2015-WSN-011), and Hanqing Li received grant support from the Research Foundation of Jinling Hospital (grant number 2014017).

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  1. Hanqing Li and Feng Li contributed equally to this work.

Authors and Affiliations

  1. Department of Hematology, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China

    Hanqing Li, Feng Li, Xiaogang Zhou, Jiangang Mei, Ping Song, Zhiming An, Qian Zhao, Xing Guo, Xuli Wang & Yongping Zhai

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  1. Hanqing Li
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  2. Feng Li
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  3. Xiaogang Zhou
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  4. Jiangang Mei
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  5. Ping Song
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  6. Zhiming An
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  7. Qian Zhao
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  8. Xing Guo
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  9. Xuli Wang
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  10. Yongping Zhai
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Correspondence to Yongping Zhai.

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The authors declare that they have no conflict of interest.

Ethical statement

This study was approved by the Clinical Research Ethics Committee of Jinling Hospital, Nanjing, China. Written consent was waived by the Ethics Committee.

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Li, H., Li, F., Zhou, X. et al. Achieving minimal residual disease-negative by multiparameter flow cytometry may ameliorate a poor prognosis in MM patients with high-risk cytogenetics: a retrospective single-center analysis. Ann Hematol 98, 1185–1195 (2019). https://doi.org/10.1007/s00277-019-03609-x

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