Real-world prognostic significance of attaining minimal residual disease negativity in newly diagnosed multiple myeloma

Abstract

The aim of the study was to evaluate the prognostic impact of minimal residual disease (MRD) in the real-world setting and the interaction between MRD and molecular risk, clinical response and autologous stem-cell transplant (ASCT). A retrospective analysis of 275 newly diagnosed multiple myeloma (NDMM) patients who achieved very good partial remission (VGPR) or better before maintenance were involved. We examined MRD status by multiparameter flow cytometry (MFC). At a median follow-up of 37 months (4-88 months), In patients who achieved ≥ VGPR, those with MRD negativity had significantly longer PFS (51 vs. 26 months; P < 0.001) and OS (Not reached: NR vs. 62 months, P < 0.001) than those with MRD positivity. MRD positivity was the independent prognostic factor for PFS with hazard ratios of 2.650 (95% CI 1.755-4.033, P < 0.001) and OS with hazard ratios of 2.122 (95% CI 1.155-3.899, P = 0.015). Achieving MRD negativity was able to ameliorate a poor prognosis associated with genetic high risk. MRD negativity was associated with better PFS regardless of ASCT treatment. MRD status was more predictable for clinical outcome than conventional clinical responses. Moreover, Sustained MRD negativity ≥ 12 or ≥ 24 months improved both PFS and OS. Patients with NDMM who achieved MRD-negative status or sustained MRD negativity had deep remission and improved clinical outcomes regardless of high-risk cytogenetics, ASCT and clinical responses in a real-world setting.

Keywords: Minimal residual disease; Multiple myeloma; Prognostic factor.

Fig. 1

Study flow chart

Fig. 2

PFS (A) and OS (D) in MM patients according to combined cytogenetic risk and MRD status. PFS (B) and OS (E) in MM patients according to combined ASCT and MRD status. PFS (C) and OS (F) in MM patients according to combined clinical response and MRD status

Fig. 3

Kaplan-Meier survival curves for PFS (A) and OS (B) according to MRD status

Fig. 4

Univariate and multivariate Cox proportional hazards regressions for PFS (A) and OS (B)

Fig. 5

Kaplan-Meier survival curves for PFS (A) and OS (B) according to sustained MRD negativity≥12 months and ≥24 months