Contributions
Abstract: PB1982
Type: Publication Only
Background
Multiple myeloma (MM) is a malignant disease characterized by an increased number of clonal (abnormal) plasma cells in the bone marrow (BM). High-dose chemotherapy followed by autologous peripheral blood stem cell transplantation (SCT) is used for the treatment of young MM patients and produces a high rate of complete remissions (CR). Recent trials with novel agent combinations alone have also resulted in high CR rates, even among old patients, high-risk patients and relapse/refractory MM. Unfortunately, most patients have a recurrences of the disease. This is due to the persistence of residual tumor cells, known as minimal residual disease (MRD), responsible for tumor relapse.
Aims
BM samples from 51 MM patients who had achieved partial or complete response or were resistant after chemotherapy, including autologous SCT, were evaluated by multiparameter flow cytometry (MFC). The study was conducted to assess the quality of remission, the correlation between the number of abnormal plasma cells of BM and other signs of disease activity, readiness of patients for autologous SCT.
Methods
The study included 51 patients MM, average age - 54 years (36-70 years), who underwent assessment of MRD from November 2014 to February 2017. According to the classification Durie-Salmon the vast majority of patients (n=40) had III stage of disease, 8 patients – II and 2 patients – I. Response to treatment was assessed according to standard EBMT criteria At the time of MRD assessment 20 patients were in CR, 8 had a partial response (PR) and 15 had a resistant disease; 5 patients had a primary MM, 3 patients were in the first relapse. Most of the patients were underwent high-dose chemotherapy with autologous SCT (n=42). Re-evaluation of MRD after therapy was managed to hold in 36 patients at a mean of 3,1 months (1,9-5,7, min-max). Analysis was performed using a FACSCantoII flow cytometer (BD) and FACSDiva software (BD). Instrument performance was checked daily by recording fluorescence intensity with calibrating beads (Cytometer Setup and Tracking from BD Biosciences). Whole BM was estimated using combination of surface and intracellular staining CD38/CD56/CD27/CD117/CD81/CD19/CD45/cytLambda/CD138/cytKappa. The sensitivity of our panel MRD is 0.01% (i.e. 10-4).
Results
Among patients in CR (n=20) confirmed the absence of MRD in 6 patients, but 14 CR patients were MRD positive. MRD was detected in all patients with PR and resistant disease (n=31). The relative content of abnormal plasma cells in CR patients with MRD positive (n = 14) was significantly lower than that in PR/resistant patients (n = 31): 0.095% (0,026-0,271%) versus 1,3% (0,203 -5,9%), pU = 0,000092. PR patients (n = 8) had a lower relative content of abnormal plasma cells (as expressed tendency), than patients with resistant disease (n = 15): 0,286% (0,177-1,129%) versus 1,48% (0, 90-8,0%), pU = 0,053. Besides the relative content of abnormal plasma cells in PR/resistant patients (n = 31) correlated with the serum M-gradient concentration (rs=0,42; p=0,019) and bone marrow plasma cells (rs=0,54, p=0,0017).
Conclusion
Currently, we can conclude that MFC could be considered as the method of choice for MRD monitoring in MM. If the disease is measured, then, indeed, enough to evaluate only the M-gradient level of serum. If the M-gradient is not defined, it is necessary to assess the number of abnormal plasma cells in the BM and strive for the high-quality responses at the time of transplantation. And also it can help us to regulate duration of maintenance therapy.
Session topic: 14. Myeloma and other monoclonal gammopathies - Clinical
Keyword(s): Multiple Myeloma, Minimal residual disease (MRD), flow cytometry, Autologous hematopoietic stem cell transplantation
Abstract: PB1982
Type: Publication Only
Background
Multiple myeloma (MM) is a malignant disease characterized by an increased number of clonal (abnormal) plasma cells in the bone marrow (BM). High-dose chemotherapy followed by autologous peripheral blood stem cell transplantation (SCT) is used for the treatment of young MM patients and produces a high rate of complete remissions (CR). Recent trials with novel agent combinations alone have also resulted in high CR rates, even among old patients, high-risk patients and relapse/refractory MM. Unfortunately, most patients have a recurrences of the disease. This is due to the persistence of residual tumor cells, known as minimal residual disease (MRD), responsible for tumor relapse.
Aims
BM samples from 51 MM patients who had achieved partial or complete response or were resistant after chemotherapy, including autologous SCT, were evaluated by multiparameter flow cytometry (MFC). The study was conducted to assess the quality of remission, the correlation between the number of abnormal plasma cells of BM and other signs of disease activity, readiness of patients for autologous SCT.
Methods
The study included 51 patients MM, average age - 54 years (36-70 years), who underwent assessment of MRD from November 2014 to February 2017. According to the classification Durie-Salmon the vast majority of patients (n=40) had III stage of disease, 8 patients – II and 2 patients – I. Response to treatment was assessed according to standard EBMT criteria At the time of MRD assessment 20 patients were in CR, 8 had a partial response (PR) and 15 had a resistant disease; 5 patients had a primary MM, 3 patients were in the first relapse. Most of the patients were underwent high-dose chemotherapy with autologous SCT (n=42). Re-evaluation of MRD after therapy was managed to hold in 36 patients at a mean of 3,1 months (1,9-5,7, min-max). Analysis was performed using a FACSCantoII flow cytometer (BD) and FACSDiva software (BD). Instrument performance was checked daily by recording fluorescence intensity with calibrating beads (Cytometer Setup and Tracking from BD Biosciences). Whole BM was estimated using combination of surface and intracellular staining CD38/CD56/CD27/CD117/CD81/CD19/CD45/cytLambda/CD138/cytKappa. The sensitivity of our panel MRD is 0.01% (i.e. 10-4).
Results
Among patients in CR (n=20) confirmed the absence of MRD in 6 patients, but 14 CR patients were MRD positive. MRD was detected in all patients with PR and resistant disease (n=31). The relative content of abnormal plasma cells in CR patients with MRD positive (n = 14) was significantly lower than that in PR/resistant patients (n = 31): 0.095% (0,026-0,271%) versus 1,3% (0,203 -5,9%), pU = 0,000092. PR patients (n = 8) had a lower relative content of abnormal plasma cells (as expressed tendency), than patients with resistant disease (n = 15): 0,286% (0,177-1,129%) versus 1,48% (0, 90-8,0%), pU = 0,053. Besides the relative content of abnormal plasma cells in PR/resistant patients (n = 31) correlated with the serum M-gradient concentration (rs=0,42; p=0,019) and bone marrow plasma cells (rs=0,54, p=0,0017).
Conclusion
Currently, we can conclude that MFC could be considered as the method of choice for MRD monitoring in MM. If the disease is measured, then, indeed, enough to evaluate only the M-gradient level of serum. If the M-gradient is not defined, it is necessary to assess the number of abnormal plasma cells in the BM and strive for the high-quality responses at the time of transplantation. And also it can help us to regulate duration of maintenance therapy.
Session topic: 14. Myeloma and other monoclonal gammopathies - Clinical
Keyword(s): Multiple Myeloma, Minimal residual disease (MRD), flow cytometry, Autologous hematopoietic stem cell transplantation