scholarly journals Multiple myeloma: Maintenance therapy after autologous hematopoietic stem cell transplantation, depending on minimal residual disease

2017 ◽  
Vol 89 (7) ◽  
pp. 25-31
Author(s):  
M V Solovyev ◽  
L P Mendeleeva ◽  
O S Pokrovskaya ◽  
M V Nareyko ◽  
M V Firsova ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Maintenance Therapy ◽  
Minimal Residual Disease ◽  
Hematopoietic Stem Cell ◽  
Residual Disease ◽  
Color Flow ◽  
Hematopoietic Stem ◽  
Minimal Residual ◽  
Risk Of Relapse

Aim. To determine the efficiency of maintenance therapy with bortezomib in patients with multiple myeloma (MM) who have achieved complete remission (CR) after autologous hematopoietic stem cell (auto-HSCT), depending on the presence of minimal residual disease (MRD). Subjects and methods. In January 2014 to February 2016, fifty-two MM patients (19 men and 33 women) aged 24 to 66 years (median 54 years), who had achieved CR after auto-HSCT, were randomized to perform maintenance therapy with bortezomib during a year. On day 100 after auto-HSCT, all the patients underwent immunophenotyping of bone marrow plasma cells by 6-color flow cytometry to detect MRD. Relapse-free survival (RFS) was chosen as a criterion for evaluating the efficiency of maintenance therapy. Results. After auto-HSCT, MRD-negative patients had a statistically significantly higher 2-year RFS rate than MRD-positive patients: 52.9% (95% confidence interval (CI), 35.5 to 70.5%) versus 37.2% (95% CI, 25.4 to 49.3%) (p=0.05). The presence of MRD statistically significantly increased the risk of relapse (odds ratio 1.7; 95% CI, 1.2 to 3.4; p=0.05). Two-year cumulative risk of relapse (using the Kaplan-Meier) after auto-HSCT did not statistically significantly differ in MRD-negative patients receiving (n=15) and not receiving (n=10) maintenance therapy with bortezomib (p=0.58). After completion of maintenance treatment, 42% of the MRD-positive patients achieved a negative status. In the MRD-positive patients who had received maintenance therapy, the average time to recurrence was 5 months longer than that in the naïve patients: 17.3 versus 12.3 months. Conclusion. The MRD status determined in MM patients who have achieved CR after auto-HSCT is an important factor for deciding on the use of maintenance therapy.

scholarly journals Evaluation of Hematopoietic Stem Cell Product As a New Site for Minimal Residual Disease By Next Generation Flow in Multiple Myeloma

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4927-4927
Author(s):  
Herbert Henrique de Melo Santos ◽  
Glaciano Ribeiro ◽  
Allan de souza Santos ◽  
Marcos Chaves ◽  
Joanna Leal ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Stem Cell ◽  
Minimal Residual Disease ◽  
Hematopoietic Stem Cell ◽  
Plasma Cell ◽  
Residual Disease ◽  
Next Generation ◽  
Hematopoietic Stem ◽  
Minimal Residual

Abstract Introduction- Next generation flow (NGF) is one of the approaches for testing multiple myeloma (MM) minimal residual disease (MRD) over conventional response assessments. Actually, bone marrow (BM) is the preference site of evaluation because of its sensitivity. Because of its invasively technic, other possible sites for MRD evaluation outside the BM have been studied. In the present study we analyzed the MRD between the BM and the hematopoietic stem cell collected product (HSC product), once the concentration of plasma cell in the HSC product could be higher than peripheric blood sample. Aims- To compare MRD quantification of plasma cell between BM and HSC product after induction from Newly Diagnosed MM(NDMM) Transplant Eligible (TE) patients (pts) exposed to daratumumab, cyclophosphamide, thalidomide and dexamethasone (Dara-CTD) protocol. Methods- The SC product and BM samples were collected after four 28 days cycles of induction therapy from pts treated with Dara-CTd protocol described before by (Crusoe E. et al. Blood 2020; 136 (supplement 1): 17-18). MRD was evaluated by next-generation flow (NGF) based in the EuroFlow® protocol. EuroFlow standards was used to identify clonality and aberrant PC immune phenotype, consisting by EuroFlow 8-color 2-tube method (MM MRD kit, Cytognos, Salamanca), with the acquisition of 5 million events each tube and then merged into a single analysis tube on approximately 10 million events. Plasma cells were identified by CD38 multiepitope and CD138. Other markers were used to detect abnormal phenotypes. For comparison of MRD results, Bland-Altman plot comparing BM-MRD and HSC product-MRD was performed. Results- The first pts was enrolled in November 2018. A total of 24 pts were included, the median age was 60 (range 37- 67 years), 23 (92%) were non-white, 5 (21%) had an R-ISS = 1, 12 (54%) had an R-ISS = 2 and 4 (16%), an R-ISS = 3. Six (25%) pts had high-risk chromosomal abnormalities [del17p, t(4;14) or t(14;16)]. To date, all pts have completed induction and 20 have received transplant. Regarding response rates, after the end of induction (cycle 4), 19 (90%) of the pts obtained > PR and 8 (38%) obtained >VGPR, including three MRD negativity by NGF. 19 pts were analyzed for MRD. Negative MRD in sensitivity <10 -5, >=10 -5 and <10 -4, >=10 -4 evaluated in bone marrow was 4/19(21%), 4/19(21%), 11/19(58%) respectively. Negative MRD in sensitivity <10 -5, >=10 -5 and <10 -4, >=10 -4 evaluated in the HSC product was 13/19(68%), 3/19(16%), 3/19(16%) respectively. Median bone marrow sensitivity 10 -4 lower quartile 10 -5 upper quartile 10 -3. Normal distribution of the differences between BM and SC product MRD was first assessed (Kolmogorov-Smirnov's p < 0.001, n = 19). Discussion-Conclusions- The use of HSC product could enhance the plasma cell concentration and may be an alternative and attractive method for MRD detection that diminished the invasiveness of repetitive bone marrow aspirations and tackling the heterogeneity distribution of MM cells. In this preliminary data the sample size did not allow to show a direct correlation between BM and HCS product. A larger sample would be needed to confirm the hypothesis. Figure 1 Figure 1. Disclosures Hungria: Amgen, BMS, Celgene, Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Support for attending meetings/travel ; Abbvie: Honoraria; Sanofi: Honoraria, Other: Support for attending meetings/travel ; Takeda: Honoraria. De Queiroz Crusoe: Janssen: Research Funding.

scholarly journals Detection of Minimal Residual Disease by Flow Cytometry for Patients with Multiple Myeloma Submitted to Autologous Hematopoietic Stem Cell Transplantation

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Suzane Dal Bó ◽  
Annelise Pezzi ◽  
Bruna Amorin ◽  
Vanessa Valim ◽  
Rosane Isabel Bittencourt ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Flow Cytometry ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Minimal Residual Disease ◽  
Cell Transplantation ◽  
Residual Disease ◽  
Hematopoietic Stem ◽  
Minimal Residual

The treatment strategy in multiple myeloma (MM) is to get complete remission followed by high-dose chemotherapy and autologous Hematopoietic Stem Cell Transplantation (HSCT). Neoplastic Plasma Cells (NPCs) are CD45-/dim, CD38+high, CD138+, CD19−, and  CD56+high in most cases. The description of this immunophenotype is of major importance as it leads to the correct identification of minimal residual disease (MRD). Samples from 44 Patients were analyzed prospectively in this study. We analyzed if the presence of MRD at three months after HSCT was predictive of relapse or death. There were 40 evaluable patients of whom 16/40 patients had MRD at three moths after HSCT and there were none in cytological relapse. The mean overall survival (OS) was 34 months and disease-free survival (RFS) was 28 months after HSCT. There was no significant difference in the log rank analysis comparing OS and the presence of MRD (P=0,611) and RFS (P=0,3106). Here, we demonstrate that three color flow cytometry (FCM) is more sensitive for MDR evaluation than cytological analyzes. However, based in our data we can not affirm that MRD is a good predictor of MM relapse or death. In conclusion, our results could be attributed to a short followup, small sample size, and over most to the inability of a three-color FCM to detect the NPC population.

scholarly journals Validation of a Sensitive Flow Cytometry Assay to Assess Minimal Residual Disease of Multiple Myeloma Cells in Apheresis Product

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5646-5646
Author(s):  
Nicholas Jones ◽  
Josette William Ragheb ◽  
Brian Ngo ◽  
David Uyeji ◽  
Anselm L. Hii
Keyword(s):  
Multiple Myeloma ◽  
Flow Cytometry ◽  
Stem Cell ◽  
Minimal Residual Disease ◽  
Patient Monitoring ◽  
Residual Disease ◽  
Cell Transplant ◽  
Flow Cytometry Assay ◽  
Color Flow ◽  
Minimal Residual

Abstract For treatment of patients with multiple myeloma (MM), flow cytometry has become a widely used and valuable method for the evaluation of minimal residual disease (MRD) in bone marrow. Use of an optimized single-tube, 10-color flow cytometry panel for assessment of MM MRD has shown to be beneficial in patient monitoring and has shown correlation to the acknowledged EuroFlow 8-color, 2-tube method. In order to further correlate levels of MM and relapse in patients, validation of a sensitive MM MRD assay that can be applied to testing for residual disease in apheresis product prior to autologous stem cell transplant, a standard treatment for patients with multiple myeloma. This approach can exhibit great value in patient monitoring and treatment. As new combination therapies are developed for treatment of multiple myeloma in concert with autologous stem cell transplantation, evaluation of MRD in apheresis will likely continue to grow in importance. The purpose of this study is to show the validation and sensitivity of a flow cytometry assay designed to detect Multiple Myeloma (MM) cells in G-CSF and other mobilized apheresis samples from human Multiple Myeloma patients. Using GSM-mobilized apheresis product, spiked with different levels of patient de-identified MM plasma cells, validation of a 10-color MM MRD panel can be evaluated, intended to mimic patient apheresis at varying levels of residual disease post treatment. As with any minimal residual disease assessment, a high number of events are required to ensure sensitivity and precision. Typically, acquisition of 3-5 x 107 events is required to ensure precision of MM MRD levels to 0.001%. Disclosures No relevant conflicts of interest to declare.

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