105例初诊多发性骨髓瘤患者微小残留病的动态监测及其预后价值

OBJECTIVE: To evaluate the prognostic value of kinetic changes in minimal residual disease (MRD) status, as well as its relationship with risk stratification, therapeutic response and treatment in patients with newly-diagnosed multiple myeloma (MM). METHODS: A total of 135 patients with newly-diagnosed MM were screened, and 105 patients who achieved VGPR or more as the best responses were included into this study. The MRD status was determined by multiparameter flow cytometry (MFC) at multiple intervals after two cycles of treatment until clinical relapse, death, or last follow-up. The statistical methods included Kaplan-Meier analysis, Cox regression, etc. RESULTS: ①In all 135 patients, 57.8% (78/135) patients achieved MRD negativity (MRD(−)) after treatment. In 105 patients who achieved VGPR and thus included in this study, the MRD(−) rate was 72.4% (76/105), with a median interval of 3 months from starting treatment to achievement of MRD(−) status. ②The 2-year PFS rate of patients with MRD(−) status was significantly higher than that of MRD(+) status (62.2% vs 41.3%, P=0.001), while MRD persistence (MRD(+)) was an independent factor for poor prognosis (multivariate analysis for PFS: P=0.044, HR=3.039, 95%CI 1.029-8.974). ③Loss of MRD(−) status (i.e., MRD reappearance) showed inferior outcomes compared with MRD sustained negative ones, the PFS was 18 months versus not reach (P<0.001) and the OS was not reach for both (P=0.002). ④The 2-year PFS and OS rates of patients with duration of MRD(−)status≥12 months were significantly higher than those of the control group (PFS: 77.7% vs 36.7%, P<0.001; OS: 96.4% vs 57.9%, P<0.001 respectively). Duration of MRD(−) status was associated with a marked reduction in risk of relapse or death (univariate analysis for PFS: P<0.001, HR=0.865, 95%CI 0.815-0.918; for OS: P=0.001, HR=0.850, 95%CI 0.741–0.915 respectively). ⑤Moreover, even in patients carrying high-risk cytogenetic abnormalities (CA) or ineligible for ASCT, MRD negativity remained its prognostic value to predict PFS (high-risk CA medianPFS: not reach vs 19 months, P=0.006; ineligible for ASCT medianPFS: not reach vs 25 months, P=0.052 respectively). ⑥Last, treatment with the bortezomib-based regimens contributed to prolonged MRD(−) duration (median MRD(−) duratio: 25 months vs 10 months, P=0.034). CONCLUSION: Our findings supported MRD(+) status as an independent poor prognostic factor in MM patients, which implicated that duration of MRD(−) status also played a significant role in evaluation of prognosis, while loss of MRD(−)status might serve as an early biomarker for relapse. Therefore, monitoring of MRD kinetics might more precisely predict prognosis, as well as guide treatment decision, especially for when to start retreatment in relapsed patients.