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.
Keywords: Cytogenetic risk stratification; Minimal residual disease; Multiparameter flow cytometry; Multiple myeloma; Prognostic factor.