scholarly journals Role of Imaging in the Evaluation of Minimal Residual Disease in Multiple Myeloma Patients

2020 ◽  
Vol 9 (11) ◽  
pp. 3519
Author(s):  
Elena Zamagni ◽  
Paola Tacchetti ◽  
Simona Barbato ◽  
Michele Cavo
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Minimal Residual Disease ◽  
Plasma Cells ◽  
Residual Disease ◽  
Imaging Techniques ◽  
Response Assessment ◽  
Response To Therapy ◽  
Whole Body ◽  
Minimal Residual

The International Myeloma Working Group (IMWG) recently introduced the evaluation of minimal residual disease (MRD) within the multiple myeloma (MM) response criteria, and MRD negativity assessed inside and outside the bone marrow is currently considered the most powerful predictor of favorable long-term outcomes. However, MRD evaluation has thus far relied on flow-cytometry or molecular-based methods, despite the limitations associated with the patchy infiltration of bone marrow (BM) plasma cells and the presence of extra-medullary (EMD). On the contrary, imaging-based sensitive response assessment through the use of functional rather than morphological whole-body (WB) imaging techniques, such as positron emission tomography with computed tomography (PET/CT) and magnetic resonance imaging (MRI), likely is a promising strategy to overcome these limitations in evaluating response to therapy and in the assessment of the MRD status in MM patients. However, despite the significant advances in the development and availability of novel functional imaging techniques for MRD evaluation, a worldwide standardization of imaging criteria for acquisition, interpretation, and reporting is yet to be determined and will be object of future investigations.

scholarly journals The Prognostic Significance of Minimal Residual Disease Detection after Induction and ASCT to the Patients with Multiple Myeloma

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4956-4956
Author(s):  
Weiqin Yao ◽  
Zhu Mingqing ◽  
Yao Feirong ◽  
Lingzhi Yan ◽  
Song Jin ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Minimal Residual Disease ◽  
Induction Therapy ◽  
Plasma Cells ◽  
Residual Disease ◽  
Prognostic Significance ◽  
Depth Of Response ◽  
Minimal Residual

Abstract Objective: In the last decade the outcome in multiple myeloma in CHINA has greatly improved due to the new, effective therapies including PIs and Imids. But responses to treatment and survival remains heterogeneous because of patient characteristic, disease biology and mechanisms of drug resistance. More and more studies have established the link between depth of response and improved PFS and OS. multiparameter-flow cytometry (MFC) is a main method to detect minimal residual disease(MRD) in myeloma. Sensitivity will be at least at 10-4 to 10-5 by 10-color MFC. Imaging techniques such as PET-CT are important for EMD and bone MRD detection. whole body DWI-MRI is a new imaging technique by mean of the apparent diffusion coefficient(ADC) which can qualify the depth of response to antineoplastic treatment. This study was designed to evaluate the prognostic significance of MRD by 10-color MFC and imaging to the MM patients after induction.Methods: 102 patients with newly diagnosed MM were enrolled at the First Affiliated Hospital of Soochow University from July 2015 to July 2017. All patients were diagnosed and the response were assessed by IMWG criteria. The median of age was 58 (31-75).There were 46 patients with IgG type , 24 IgA , 14 light chain, 18 others. 34 Patients in ISS stageⅠ,34 in stage Ⅱ, 30 in stage Ⅲ. All patients received 4-6 cycles of triplet bortezomib based or lenalidomide based induction therapy. Transplantation available patients received APBSCT with BUCY condition followed by 4-6 cycles of bortezomib based or lenalidomide based consolidation which were given to transplantation unavailable patients too. Lenalidomide and thalidomide were used for over 2y of maintenance therapy. Bone marrow aspirates for MRD imaging MRD assessment were obtained at the end of induction and 1year after ASCT.The median of follow-up was 13 (2-29) months.Results: According to MRD by MFC and imaging after induction therapy and 1 year after ASCT, the patients were divided into different groups. MFC negativity was 33%(29/88) after induction therapy compared with 63%(32/51) after ASCT (X2=11.636,P=0.001). After induction therapy, the median PFS was 22 months for MRD positive group compared with not reached with MRD negative group by MFC (P=0.042) in patients with very good partial remission(VGPR) and above. The 2 years PFS was 100% for those with MRD negative compared with 60% for MRD positive by imaging. The 2 years PFS was 80% for those have multiclonal normal plasma cells compared with 52.6% for those without. The median PFS was not reached for MFC MRD negative patients 1 year after ASCT compared with 20 months for positive patients. (P=0.002). Multivariate analysis including high risk cytogenetics(17p-, t(4;14), t(14;16)), sex, age, ISS, chemotherapy, ASCT, CR/VGPR, normal PCs showed that the MFC MRD and ASCT were independent prognostic factor.Conclusions: Patients with MFC MRD negative after induction therapy or ASCT is a better prognostic marker than CR or even the best marker. Imaging MRD negativity and the appearance of normal plasma cells in the bone marrow suggests a better prognosis.We will have a try to do more research on overall survival(OS),include longer follow-up and a larger number of patients enrolled. Figure. Figure. Disclosures No relevant conflicts of interest to declare.

scholarly journals What to do with minimal residual disease testing in myeloma

Hematology ◽  
2019 ◽  
Vol 2019 (1) ◽  
pp. 137-141
Author(s):  
Elisabet E. Manasanch
Keyword(s):  
Bone Marrow ◽  
Minimal Residual Disease ◽  
Residual Disease ◽  
Body Position ◽  
Progression Free Survival ◽  
Response Assessment ◽  
Routine Care ◽  
Whole Body ◽  
Position Emission Tomography ◽  
Minimal Residual

Abstract The role and use of minimal residual disease (MRD) testing has changed significantly over the past few years as it has become part of the routine care for response assessment in multiple myeloma. The most widely used standardized methods to assess MRD in myeloma in the bone marrow are multicolor flow cytometry and next-generation sequencing. Importantly, the depth of MRD negativity in the bone marrow correlates with improved progression-free survival and overall survival in myeloma. Whole-body position emission tomography–computed tomography and magnetic resonance imaging are also used to evaluate patchy and extramedullary disease, which may not be readily visible through bone marrow assessment. This article reviews a clinical case in which MRD testing, both in bone marrow and in functional imaging, is part of the standard of care. It also reviews the different modalities of MRD testing and current practice guidelines. Finally, patients with myeloma may be tested for MRD after treatment because this is part of the routine response assessment according to International Myeloma Working Group criteria and correlates with clinical outcomes. Important questions such as when to stop therapy for sustained MRD-negative patients or whether to change treatments for patients who go from MRD negative to positive without other evidence of disease relapse are being evaluated in clinical trials and remain controversial.

scholarly journals Pharmacogenetics of minimal residual disease response in children with B-precursor acute lymphoblastic leukemia: a report from the Children's Oncology Group

Blood ◽  
2008 ◽  
Vol 111 (6) ◽  
pp. 2984-2990 ◽  
Author(s):  
Stella M. Davies ◽  
Michael J. Borowitz ◽  
Gary L. Rosner ◽  
Kristin Ritz ◽  
Meenakshi Devidas ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
Minimal Residual Disease ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Response To Therapy ◽  
Oncology Group ◽  
Risk Status ◽  
Prognostic Features ◽  
Minimal Residual

Abstract Minimal residual disease (MRD) as a marker of antileukemic drug efficacy is being used to assess risk status and, in some cases, to adjust the intensity of therapy. Within known prognostic categories, the determinants of MRD are not known. We measured MRD by flow cytometry at day 8 (in blood) and at day 28 (in bone marrow) of induction therapy in more than 1000 children enrolled in Pediatric Oncology Group therapy protocols 9904, 9905, and 9906. We classified patients as “best risk” if they had cleared MRD by day 8 of therapy and as “worst risk” if they had MRD remaining in bone marrow at day 28, and tested whether MRD was related to polymorphisms in 16 loci in genes hypothesized to influence response to therapy in acute lymphoblastic leukemia (ALL). After adjusting for known prognostic features such as presence of the TEL-AML1 rearrangement, National Cancer Institute (NCI) risk status, ploidy, and race, the G allele of a common polymorphism in chemokine receptor 5 (CCR5) was associated with more favorable MRD status than the A allele (P = .009, logistic regression), when comparing “best” and “worst” risk groups. These data are consistent with growing evidence that both acquired and host genetics influence response to cancer therapy.

Analysis of minimal residual disease in bone marrow by NGF and in peripheral blood by mass spectrometry in newly diagnosed multiple myeloma patients enrolled in the GEM2012MENOS65 clinical trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 8010-8010
Author(s):  
Noemi Puig ◽  
Bruno Paiva ◽  
Teresa Contreras ◽  
M. Teresa Cedena ◽  
Laura Rosiñol ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Multiple Myeloma ◽  
Bone Marrow ◽  
Minimal Residual Disease ◽  
Peripheral Blood ◽  
Prognostic Value ◽  
Residual Disease ◽  
Newly Diagnosed ◽  
Time Points ◽  
Minimal Residual

8010 Background: Analysis of minimal residual disease (MRD) in the bone marrow (BM) of patients with multiple myeloma (MM) is accepted by the IMWG to evaluate treatment efficacy and is a well-established prognostic factor. However, there is an unmet need to explore the clinical value of MRD in peripheral blood (PB). Methods: Newly diagnosed MM patients enrolled in the GEM2012MENOS65 trial received six induction (Ind) cycles of bortezomib, lenalidomide, and dexamethasone (VRD) followed by autologous stem cell transplantation (ASCT) and 2 further cycles of consolidation (Cons) with VRD. MRD was analyzed in BM using Next Generation Flow (NGF) and in serum by Mass Spectrometry (MS) using IgG/A/M, κ, λ, free κ and free λ specific beads, both after Ind, at day 100 after ASCT, and after Cons. Sequential samples from the first 184 patients were analyzed. Results: Results of both methods were in agreement (NGF+/MS+ and NGF-/MS-) in 83% of cases post-Ind (152/184), 80% post-ASCT (139/174) and 76% post-Cons (128/169). Stratifying by the log range of MRD by NGF, discordances (NGF+/MS- and NGF-/MS+) seemed to increase at the lower MRD ranges, being 22%, 21% and 19% from ≥10−5 to <10−4 and 21%, 21%, 23% at ≥x10−6(post-Ind, ASCT and Cons, respectively). Analysis of discordances showed that they could be partly explained by the higher percentages of cases found to be positive by MS as compared by NGF at part of the time-points analyzed and at each log range of MRD. From ≥10−5 to <10−4, MRD was detected by NGF in 36%, 28%, 20% of cases post-Ind, ASCT and Cons, respectively vs MS in 37%, 29%, 21% of them; at ≥x10−6, NGF was positive in 11%, 14%, 19% of cases vs MS in 23%, 19% and 16% of them. Considering NGF as a reference, the negative predictive value (NPV) of MS per MRD range (≥10−5 to <10−4 and ≥x10−6, respectively) was: post-Ind: 83% (p<0,0001), 94% (p=0,034); post-ASCT 86% (p<0,0001), 90% (p=0,022); post-Cons 89% (p<0,0001), 85% (p=0,0469). Despite these discordances, the prognostic value of each technique in terms of undetectable MRD and progression-free survival (PFS) was consistent at all time-points (Table) and further, discordant cases (NGF+/MS- and NGF-/MS+) did not display a significantly different PFS as compared to NGF-/MS- cases. Conclusions: The results of MRD assessed by NGF in BM and by MS in PB show a significant concordance and are associated with a similar prognostic value analyzed in terms of PFS. Given its high NPV, MRD in peripheral blood by MS provides a gateway for BM aspiration/biopsy and MRD assessment by NGF.[Table: see text]

scholarly journals New criteria for response assessment: role of minimal residual disease in multiple myeloma

Blood ◽  
2015 ◽  
Vol 125 (20) ◽  
pp. 3059-3068 ◽  
Author(s):  
Bruno Paiva ◽  
Jacques J. M. van Dongen ◽  
Alberto Orfao
Keyword(s):  
Multiple Myeloma ◽  
Minimal Residual Disease ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Response Assessment ◽  
Baseline Risk ◽  
Multiparameter Flow Cytometry ◽  
New Criteria ◽  
Minimal Residual

Abstract Assessment of minimal residual disease (MRD) is becoming standard diagnostic care for potentially curable neoplasms such as acute lymphoblastic leukemia. In multiple myeloma (MM), the majority of patients will inevitably relapse despite achievement of progressively higher complete remission (CR) rates. Novel treatment protocols with inclusion of antibodies and small molecules might well be able to further increase remission rates and potentially also cure rates. Therefore, MRD diagnostics becomes essential to assess treatment effectiveness. This review summarizes reports from the past 2 decades, which demonstrate that persistent MRD by multiparameter flow cytometry, polymerase chain reaction, next-generation sequencing, and positron emission tomography/computed tomography, predicts significantly inferior survival among CR patients. We describe the specific features of currently available techniques for MRD monitoring and outline the arguments favoring new criteria for response assessment that incorporate MRD levels. Extensive data indicate that MRD information can potentially be used as biomarker to evaluate the efficacy of different treatment strategies, help on treatment decisions, and act as surrogate for overall survival. The time has come to address within clinical trials the exact role of baseline risk factors and MRD monitoring for tailored therapy in MM, which implies systematic usage of highly sensitive, cost-effective, readily available, and standardized MRD techniques.

scholarly journals Minimal residual disease in multiple myeloma: why, when, where

Hematology ◽  
2021 ◽  
Vol 2021 (1) ◽  
pp. 37-45
Author(s):  
Andrew J. Yee ◽  
Noopur Raje
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Flow Cytometry ◽  
Clinical Practice ◽  
Minimal Residual Disease ◽  
Residual Disease ◽  
Limit Of Detection ◽  
Improved Outcomes ◽  
Future Clinical Practice ◽  
Minimal Residual

Abstract Improvements in multiple myeloma therapy have led to deeper responses that are beyond the limit of detection by historical immunohistochemistry and conventional flow cytometry in bone marrow samples. In parallel, more sensitive techniques for assessing minimal residual disease (MRD) through next-generation flow cytometry and sequencing have been developed and are now routinely available. Deep responses when measured by these assays correspond with improved outcomes and survival. We review the data supporting MRD testing as well as its limitations and how it may fit in with current and future clinical practice.

scholarly journals Clinical implications of loss of bone marrow minimal residual disease negativity in multiple myeloma

2021 ◽  
Author(s):  
Meera Mohan ◽  
Samantha Kendrick ◽  
Aniko Szabo ◽  
Naveen K Yarlagadda ◽  
Dinesh Atwal ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Minimal Residual Disease ◽  
Residual Disease ◽  
Progression Free Survival ◽  
Response To Treatment ◽  
Clinical Relapse ◽  
Landmark Analyses ◽  
Minimal Residual

Multiple myeloma (MM) patients frequently attain a bone marrow (BM) minimal residual disease (MRD) negativity status in response to treatment. We identified 568 patients who achieved BM MRD negativity following autologous stem cell transplantation (ASCT) and maintenance combination therapy with an immunomodulatory agent and a proteasome inhibitor. BM MRD was evaluated by next generation flow cytometry (sensitivity of 10-5 cells) at 3 to 6 months intervals. With a median follow up of 9.9 years from diagnosis (range, 0.4 - 30.9), 61% of patients maintained MRD negativity, while 39% experienced MRD conversion at a median of 6.3 years (range, 1.4 - 25). The highest risk of MRD conversion occurred within the first 5 years after treatment and was observed more often in patients with abnormal metaphase cytogenetic abnormalities (95%vs. 84%; P = 0.001). MRD conversion was associated with a high risk of relapse and preceded it by a median of 1.0 year (range, 0 - 4.9). However, 27% of MRD conversion positive patients had not yet experienced a clinical relapse with a median follow-up of 9.3 years (range, 2.2 - 21.2). Landmark analyses using time from ASCT revealed patients with MRD conversion during the first 3 years had an inferior overall and progression-free survival compared to patients with sustained MRD negativity. MRD conversion correctly predicted relapse in 70%, demonstrating the utility of serial BM MRD assessment to complement standard laboratory and imaging to make informed salvage therapy decisions.

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