| Background and objective:Multiple myeloma(MM)is a heterogenous plasma cell malignancy,and its incidence ranks second in the hematological tumor.In the past decade,due to the wide application of new drugs and autologous hematopoietic stem cell transplantation(ASCT),the therapeutic effect of MM patients has been significantly improved.However,multiple myeloma is still a fatal disease that cannot be cured.The main reason is that there are still a small number of myeloma cells that have not been detected in the patient after treatment,that is,minimal residual disease(MRD).MRD is mostly resistant clones and is the root cause of refractory or relapse.Recently,multiple clinical trials have used multiparameter flow cytometry(MFC)or molecular biology methods(such as polymerase chain reaction or next-generation sequencing technology)to detect MRD,suggesting that MRD is of great significance in the prognosis of MM.However,most of the current research on MRD mainly analyzes the therapeutic effect and survival of clinical trials by detecting MRD status,and does not solve the related problems in specific clinical practice such as different cytogenetic abnormalities(CA),different treatment options(including ASCT,maintenance therapy)on the negative conversion of MRD and its duration.The purpose of the present study was to investigate the dynamic changes of minimal residual disease in newly diagnosed multiple myeloma(NDMM)and its relationship with clinical features,treatment and survival.Methods:The clinical data of 131 cases with NDMM who were admitted to the Cancer Center of the First Hospital of Jilin University from July 2013 to December 2017 were retrospectively analyzed.The clinical features and survival of MRD-negative group and non-negative group were compared.The relationship between MRD status and therapeutic response was explored.The prognostic value of MRD status combined with different clinical features in MM was clarified.Results:1.In 131 patients with NDMM,the negative rate of MRD was 63.4%(83/131).The rate of MRD conversion in patients receiving induction therapy with bortezomib(Btz),ASCT and maintenance therapy was significantly higher than that in the control group(P=0.014,0.017,0.004).2.In 131 patients with regular medical follow-up,the PFS and OS of the MRD-negative group were significantly longer than those of the non-negative group(P=0.002,0.050).Multivariate analysis of prognosis of 87 patients with NDMM have demonstrated that only MRD-positive is an independent adverse prognostic factor affecting PFS(P<0.001)and OS(P=0.005).While,high risk cytogenetic abnormalities(HRCA)is only an independent poor prognostic factor affecting PFS(P=0.049).3.The median time to MRD negative in 83 patients with MRD negative was 4 months after treatment.There was no significant difference in PFS and OS between the time to MRD-negative ≤ 4 months group and > 4 month group(P>0.05).4.Among the 83 MRD negative patients,the PFS and OS of the patients sustained MRD negative were significantly longer than those lost MRD negative status(P<0.001,P=0.003).The OS of patients with MRD negative duration of ≥ 6 months was obviously longer than that of patients with < 6 months(P<0.001),but there was no significant statistical difference in PFS between the two groups(P>0.05).While,there was a significant statistical difference in both PFS and OS between patients with MRD negative duration ≥ 12 months and patients < 12 months(P<0.001,P<0.001).The risk of relapse/death was significantly reduced with prolonged MRD negative duration(PFS: HR=0.886,P<0.001;OS: HR=0.844,P<0.001).5.Patients with HRCA were divided into two groups according to the MRD status.PFS and OS in patients with MRD-negative were significantly better than those with MRD-positive group(P<0.001,P<0.001).Patients with MRD negative status were divided into two groups according to the cytogenetic abnormalities.However,neither PFS nor OS seemed to have a significant statistical difference between the two groups(P>0.05).For patients carrying standard risk cytogenetic abnormalities(SRCA),but MRD positive,their PFS and OS were similar as those MRD-negative patients carrying HRCA(P>0.05).6.There were no statistically significant differences in PFS and OS between the MRD-negative patients with or without bortezomib(P>0.05).There were also no statistically significant differences in PFS and OS between the MRD-negative patients who received or not received ASCT(P>0.05).However,in patients with MRD negative status,the OS in the maintenance group was obviously longer than that in the non-maintenance group(P=0.003),but there was no significant statistical difference in PFS between the two groups(P>0.05).Conclusions:1.MRD is an independent prognostic factor for both progression free survival and overall survival in NDMM patients.MRD negative duration is another important prognostic factor.2.Loss of MRD negative status can significantly shorten the patient’s progression free survival and overall survival,which may become an early indicator of recurrence.3.HRCA patients with MRD can bring survival advantages.4.Induction therapy with bortezomib,treatment with ASCT and maintenance therapy can improve the rate of MRD-negative,which may improve prognosis.In particular,maintenance therapy can obviously prolong overall survival even in patients with MRD negative status. |
