scholarly journals Front-line Management of Multiple Myeloma – How Can We Best Assess the Depth of Response?

2015 ◽  
Vol 11 (2) ◽  
pp. 105
Author(s):  
Michel Delforge ◽  

The outcome for patients with multiple myeloma (MM) is gradually improving due to the introduction of several new agents with strong antimyeloma activity. Both younger (transplant-eligible) and elderly patients benefit from this therapeutic progress. Although complete remission can be achieved in a significant group of MM patients, the majority of these patients will relapse because of the persistence of minimal residual disease. In this editorial, we discuss the different assays for response assessment in myeloma together with their limitations and clinical importance.

HemaSphere ◽  
2019 ◽  
Vol 3 (S1) ◽  
pp. 268
Author(s):  
J. Martinez-Lopez ◽  
S. Wong ◽  
N. Shah ◽  
N. Bahri ◽  
T. Martin ◽  
...  

Author(s):  
Alessandro Gozzetti ◽  
Monica Bocchia

: Minimal residual disease (MRD) detection represents a great advancement in multiple myeloma. New drugs are now available that increase depth of response. The International Myeloma Working Group recommends the use of next-generation flow cytometry (NGF) or next-generation sequencing (NGS) to search for MRD in clinical trials. Best sensitivity thresholds have to be confirmed, as well as timing to detect it. MRD has proven as the best prognosticator in many trials and promises to enter also in clinical practice to guide future therapy.


2017 ◽  
Vol 35 (25) ◽  
pp. 2900-2910 ◽  
Author(s):  
Juan-Jose Lahuerta ◽  
Bruno Paiva ◽  
Maria-Belen Vidriales ◽  
Lourdes Cordón ◽  
Maria-Teresa Cedena ◽  
...  

Purpose To perform a critical analysis on the impact of depth of response in newly diagnosed multiple myeloma (MM). Patients and Methods Data were analyzed from 609 patients who were enrolled in the GEM (Grupo Español de Mieloma) 2000 and GEM2005MENOS65 studies for transplant-eligible MM and the GEM2010MAS65 clinical trial for elderly patients with MM who had minimal residual disease (MRD) assessments 9 months after study enrollment. Median follow-up of the series was 71 months. Results Achievement of complete remission (CR) in the absence of MRD negativity was not associated with prolonged progression-free survival (PFS) and overall survival (OS) compared with near-CR or partial response (median PFS, 27, 27, and 29 months, respectively; median OS, 59, 64, and 65 months, respectively). MRD-negative status was strongly associated with prolonged PFS (median, 63 months; P < .001) and OS (median not reached; P < .001) overall and in subgroups defined by prior transplantation, disease stage, and cytogenetics, with prognostic superiority of MRD negativity versus CR particularly evident in patients with high-risk cytogenetics. Accordingly, Harrell C statistics showed higher discrimination for both PFS and OS in Cox models that included MRD (as opposed to CR) for response assessment. Superior MRD-negative rates after different induction regimens anticipated prolonged PFS. Among 34 MRD-negative patients with MM and a phenotypic pattern of bone marrow involvement similar to monoclonal gammopathy of undetermined significance at diagnosis, the probability of “operational cure” was high; median PFS was 12 years, and the 10-year OS rate was 94%. Conclusion Our results demonstrate that MRD-negative status surpasses the prognostic value of CR achievement for PFS and OS across the disease spectrum, regardless of the type of treatment or patient risk group. MRD negativity should be considered as one of the most relevant end points for transplant-eligible and elderly fit patients with MM.


Blood ◽  
2015 ◽  
Vol 125 (20) ◽  
pp. 3059-3068 ◽  
Author(s):  
Bruno Paiva ◽  
Jacques J. M. van Dongen ◽  
Alberto Orfao

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.


Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4956-4956
Author(s):  
Weiqin Yao ◽  
Zhu Mingqing ◽  
Yao Feirong ◽  
Lingzhi Yan ◽  
Song Jin ◽  
...  

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.


Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3487-3487
Author(s):  
Kyle J. Thulien ◽  
Andrew R. Blech ◽  
Tony Reiman ◽  
Linda M. Pilarski

Abstract In multiple myeloma (MM), new therapeutic strategies utilize the proteasome inhibitor bortezomib (Velcade) and the thalidomide immunomodulatory analog lenalidomide (Revlimid). While promising, MM invariably recurs, necessitating a better understanding of the malignant cells that persist during periods of complete remission (CR). In MM, minimal residual disease (MRD) is a valuable prognostic indicator for predicting time to relapse. There are no published studies to quantify the MRD or malignant cells that resist Velcade or Revlimid. In MM, the uniquely rearranged IgH VDJ gene provides a molecular signature. PCR strategies incorporating amplification of genomic DNA using patient specific primers provide a means to quantify MRD in MM patients. To date, the patient cohort tested included three MM patients achieving CR as part of a randomized trial for Revlimid plus dexamethasone, one MM patient with CR in response to dexamethasone (dex) alone, and two MM patients achieving CR after Velcade. All of the CR patients had clonotypic VDJ mRNA transcripts in BM by RT-PCR. Analysis of genomic DNA (gDNA) quantifies the number of malignant cells, as each cell has only one copy of the MM IgH VDJ. Three strategies were employed to quantify the extent of minimal disease during CR to these agents: semi-quantitative PCR analysis of purified gDNA from BM aspirates, quantitative realtime PCR using SYBR Green, and PCR analysis of cells captured from BM aspirate slides (laser pressure catapulting). 1) The semi-quantitative method measures the amount of gDNA template in the PCR reaction required to attain a positive signal, independent of cell type or morphology. 2) The quantitative PCR confirms method 1 by plotting rate of amplification of gDNA for a control sequence as compared to the clonotypic sequence, to calculate the frequency of all clonotypic MM cells in BM. 3) Laser pressure catapulting of BM cells from slide preparations provides a measure that most closely approximates the in vivo situation because it does not introduce potential artifacts arising from purification of cells and DNA that could confound interpretation of the results, and enables morphological identification of the cell types harboring clonotypic IgH VDJ genes. BM aspirate slides were viewed and numerous small patches of cells (8–15 cells) were captured into individual tubes for PCR analysis. Overall, we found that CR patients treated with Revlimid+ Dex have a 100 fold lower frequency of clonotypic MM cells (requiring 1.59e5 cells to detect a positive signal) than did the MM patient in CR from dex (detectable in 1.01e3 cells), indicating that Revlimid substantially reduced, but did not eradicate the malignant clone. Furthermore, for one patient, for whom sequential BM samples were available, the clonal frequency continued to decrease over time. Patients in CR after Velcade treatment have MM cells detectable in 1.32e4 cells. Both therapies exert more depletion as compared to dex alone. Larger patient cohorts are being analyzed to further quantify levels of MRD achieved in response to these agents.


Leukemia ◽  
1999 ◽  
Vol 13 (4) ◽  
pp. 641-644 ◽  
Author(s):  
F Genevieve ◽  
M Zandecki ◽  
J-L Laï ◽  
B Hennache ◽  
J-L Faucompre ◽  
...  

2020 ◽  
Vol 9 (11) ◽  
pp. 3519
Author(s):  
Elena Zamagni ◽  
Paola Tacchetti ◽  
Simona Barbato ◽  
Michele Cavo

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.


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