Browse
Submit Data
Databases
API
Help

Dataset Information

30 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Minimal Residual Disease in Multiple Myeloma: State of the Art and Future Perspectives.

ABSTRACT: Minimal residual disease (MRD) detection represents a sensitive tool to appropriately measure the response obtained with therapies for multiple myeloma (MM). The achievement of MRD negativity has superseded the conventional complete response (CR) and has been proposed as a surrogate endpoint for progression-free survival and overall survival. Several techniques are available for the detection of MRD inside (next-generation sequencing, flow cytometry) and outside (PET/CT, magnetic resonance) the bone marrow, and their complementary use allows a precise definition of the efficacy of anti-myeloma treatments. This review summarizes MRD data and results from previous clinical trials, highlights open issues related to the role of MRD in MM and discusses how MRD could be implemented in clinical practice to inform on patient prognosis and drive therapeutic decisions.

SUBMITTER: Mina R

PROVIDER: S-EPMC7408660 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Minimal Residual Disease in Multiple Myeloma: State of the Art and Future Perspectives.

Mina Roberto R Oliva Stefania S Boccadoro Mario M

Journal of clinical medicine 20200707 7

Minimal residual disease (MRD) detection represents a sensitive tool to appropriately measure the response obtained with therapies for multiple myeloma (MM). The achievement of MRD negativity has superseded the conventional complete response (CR) and has been proposed as a surrogate endpoint for progression-free survival and overall survival. Several techniques are available for the detection of MRD inside (next-generation sequencing, flow cytometry) and outside (PET/CT, magnetic resonance) the ...[more]

PMID: 32645952

Similar Datasets

Clinical Applications and Future Directions of Minimal Residual Disease Testing in Multiple Myeloma.

Project description:In the last years, the life expectancy of multiple myeloma (MM) patients has substantially improved thanks to the availability of many new drugs. Our ability to induce deep responses has improved as well, and the treatment goal in patients tolerating treatment moved from the delay of progression to the induction of the deepest possible response. As a result of these advances, a great scientific effort has been made to redefine response monitoring, resulting in the development and validation of high-sensitivity techniques to detect minimal residual disease (MRD). In 2016, the International Myeloma Working Group (IMWG) updated MM response categories defining MRD-negative responses both in the bone marrow (assessed by next-generation flow cytometry or next-generation sequencing) and outside the bone marrow. MRD is an important factor independently predicting prognosis during MM treatment. Moreover, using novel combination therapies, MRD-negative status can be achieved in a fairly high percentage of patients. However, many questions regarding the clinical use of MRD status remain unanswered. MRD monitoring can guide treatment intensity, although well-designed clinical trials are needed to demonstrate this potential. This mini-review will focus on currently available techniques and data on MRD testing and their potential future applications.

| S-EPMC7006453 | biostudies-literature

Minimal Residual Disease Assessment Within the Bone Marrow of Multiple Myeloma: A Review of Caveats, Clinical Significance and Future Perspectives.

Project description:There is an increasing clinical interest in the measure and achievement of minimal residual disease (MRD) negativity in the bone marrow of Multiple Myeloma (MM) patients, as defined equally either by Multicolor Flow Cytometry (MFC) or by Next Generation Sequencing (NGS) technologies. At present, modern technologies allow to detect up to one on 104 or on 105 or even on 106 cells, depending on their throughput. MFC approaches, which have been progressively improved up to the so-called Next Generation Flow (NGF), and NGS, which proved clear advantages over ASO-PCR, can detect very low levels of residual disease in the BM. These methods are actually almost superimposable, in terms of MRD detection power, supporting the lack of unanimous preference for either technique on basis of local availability. However, some technical issues are still open: the optimal assay to use to detect either phenotype (e.g., next generation multidimensional flow cytometry, imaging) or genotype aberrations (e.g., ASO-RQ PCR, digital droplet PCR, NGS) and their standardization, the sample source (BM or peripheral blood, PB) and its pre-processing (red-cell lysis vs. Ficoll, fresh vs. frozen samples, requirement of CD138+ cells enrichment). Overall, MRD negativity is considered as the most powerful predictor of favorable long-term outcomes in MM and is likely to represent the major driver of treatment strategies in the near future. In this manuscript, we reviewed the main pitfalls and caveats of MRD detection within bone marrow in MM patients after front-line therapy, highlighting the improving of the currently employed technology and describing alternative methods for MRD testing in MM, such as liquid biopsy.

| S-EPMC6710454 | biostudies-literature

Minimal Residual Disease in Multiple Myeloma: Current Landscape and Future Applications With Immunotherapeutic Approaches.

Project description:The basic principle that deeper therapeutic responses lead to better clinical outcomes in cancer has emerged technologies capable of detecting rare residual tumor cells. The need for ultra-sensitive approaches for minimal residual disease (MRD) detection is particularly evident in Multiple Myeloma (MM), where patients will ultimately relapse despite the achievement of complete remission, which is commonplace due to remarkable therapeutic advances. Consequently, current response criteria on MM have been amended based on MRD status and MRD negativity is now considered the most dominant prognostic factor and the most valuable indicator for a subsequent relapse. However, there are particular limitations and several aspects for MRD assessment that remain open. This review summarizes current data on MRD in the clinical management of MM, highlights open issues and discusses the challenges and the endless opportunities arising for both patients and clinicians. Furthermore, it focuses on the current status of MRD in clinical trials, its dynamics in addressing debatable aspects in the clinical handling and its potential role as the prevailing factor for future MRD-driven tailored therapies.

| S-EPMC7267070 | biostudies-literature

Minimal residual disease in multiple myeloma: current status.

Project description:Multiple myeloma (MM) is a treatable plasma cell cancer with no cure. Clinical evidence shows that the status of minimal residual disease (MRD) after treatment is an independent prognostic factor of MM. MRD indicates the depth of post-therapeutic remission. In this review article, we outlined the major clinical trials that have determined the prognostic value of MRD in MM. We also reviewed different methods that were used for MM MRD assessment. Most important, we reviewed our current understanding of MM MRD biology. MRD studies strongly indicate that MRD is not a uniform declination of whole MM tumor population. Rather, MM MRD exhibits unique signatures of cytogenetic aberration and gene expression profiles, unlike those of MM cells before therapy. Diagnostic high-risk MM and low-risk MM exhibited a diversity of MRD features. Clonal evaluation may occur at the MRD stage in MM. The dynamics from the diagnostic MM to MRD correlate with the disease prognosis. Lastly, on the aspect of omics, we performed data-based analysis to address the biological features underlying the course of diagnostic-to-MRD MM. To summarize, the MRD stage of disease represents a critical step in MM pathogenesis and progression. Demonstration of MM MRD biology should help us to deal with the curative difficulties.

| S-EPMC8515655 | biostudies-literature

Minimal residual disease in multiple myeloma: why, when, where.

Project description: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.

| S-EPMC8791109 | biostudies-literature

Minimal Residual Disease Assessment in Multiple Myeloma Patients: Minimal Disease With Maximal Implications.

Project description:Multiple Myeloma (MM), the second most common hematologic malignancy, has been the target of many therapeutic advances over the past two decades. The introduction of novel agents, such as proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies, along with autologous hematopoietic stem cell transplantation (ASCT) in the current standard of care, has increased the median survival of myeloma patients significantly. Nevertheless, a curative treatment option continues to elude us, and MM remains an incurable disease, with patients relapsing even after achieving deep conventionally defined responses, underscoring the need for the development of sensitive methods that will allow for proper identification and management of the patients with a higher probability of relapse. Accurate detection of Minimal Residual Disease (MRD) from a bone marrow biopsy represents a relatively new approach of evaluating response to treatment with data showing clear benefit from obtaining MRD(-) status at any point of the disease course. As life expectancy for patients with MM continues to increase and deep responses are starting to become the norm, establishing and refining the role of MRD in the disease course is more relevant than ever. This review examines the different methods used to detect MRD and discusses future considerations regarding the implementation in day-to-day clinical practice and as a prospective primary endpoint for clinical trials.

| S-EPMC8825476 | biostudies-literature

Transcriptional profiling of microglia; current state of the art and future perspectives

Project description:Microglia are the tissue macrophages of the central nervous system (CNS) and the first to respond to CNS dysfunction and disease. Gene expression profiling of microglia during development, under homeostatic conditions and in the diseased CNS provided insight in microglia functions and changes thereof. Single cell sequencing studies further contributed to our understanding of microglia heterogeneity in relation to age, sex and CNS disease. Recently, single nucleus gene expression profiling was performed on (frozen) CNS tissue. Transcriptomic profiling of CNS tissues by (single) nucleus RNA-sequencing has the advantage that it can be applied to archived and well stratified frozen specimens. Here, we give an overview of the significant advances recently made in microglia transcriptional profiling. In addition, we present matched cellular and nuclear microglia RNA-seq datasets we generated from mouse and human CNS tissue to compare cellular versus nuclear transcriptomes from fresh and frozen samples. We demonstrate that microglia can be similarly profiled with cell and nucleus profiling, and importantly also with nuclei isolated from frozen tissue. Nuclear microglia transcriptomes are a reliable proxy for cellular transcriptomes. Interestingly, lipopolysaccharide- (LPS)-induced changes in gene expression were even more pronounced in the nuclear transcriptome. In addition, heterogeneity in microglia observed in fresh samples is similarly detected in frozen nuclei of the same donor. Together, these results show that microglia nuclear RNAs obtained from frozen CNS tissue are a reliable proxy for microglia gene expression and cellular heterogeneity and may prove an effective strategy to study of the role of microglia in neuropathology.

2019-08-10 | GSE135618 | GEO

Defining the undetectable: The current landscape of minimal residual disease assessment in multiple myeloma and goals for future clarity.

Project description:Multiple Myeloma, the second most prevalent hematologic malignancy, yet lacks an established curative therapy. However, overall response rate to modern four-drug regimens approaches 100%. Major efforts have thus focused on the measurement of minute quantities of residual disease (minimal residual disease or MRD) for prognostic metrics and therapeutic response evaluation. Currently, MRD is assessed by flow cytometry or by next generation sequencing to track tumor-specific immunoglobulin V(D)J rearrangements. These bone marrow-based methods can reach sensitivity thresholds of the identification of one neoplastic cell in 1,000,000 (10-6). New technologies are being developed to be used alone or in conjunction with established methods, including peripheral blood-based assays, mass spectrometry, and targeted imaging. Data is also building for MRD as a surrogate endpoint for overall survival. Here, we will address the currently utilized MRD assays, challenges in validation across labs and clinical trials, techniques in development, and future directions for successful clinical application of MRD in multiple myeloma.

| S-EPMC9928431 | biostudies-literature

CAR T-Cells in Multiple Myeloma: State of the Art and Future Directions.

Project description:Despite recent therapeutic advances, the prognosis of multiple myeloma (MM) patients remains poor. Thus, new strategies to improve outcomes are imperative. Chimeric antigen receptor (CAR) T-cell therapy has changed the treatment landscape of B-cell malignancies, providing a potentially curative option for patients who are refractory to standard treatment. Long-term remissions achieved in patients with acute lymphoblastic leukemia and Non-Hodgkin Lymphoma encouraged its further development in MM. B-cell maturation antigen (BCMA)-targeted CAR T-cells have established outstanding results in heavily pre-treated patients. However, several other antigens such as SLAMF7 and CD44v6 are currently under investigation with promising results. Idecabtagene vicleucel is expected to be approved soon for clinical use. Unfortunately, relapses after CAR T-cell infusion have been reported. Hence, understanding the underlying mechanisms of resistance is essential to promote prevention strategies and to enhance CAR T-cell efficacy. In this review we provide an update of the most recent clinical and pre-clinical data and we elucidate both, the potential and the challenges of CAR T-cell therapy in the future.

| S-EPMC7399644 | biostudies-literature

Functional Imaging for Therapeutic Assessment and Minimal Residual Disease Detection in Multiple Myeloma.

Project description:Serum markers and bone marrow examination are commonly used for monitoring therapy response in multiple myeloma (MM), but this fails to identify minimal residual disease (MRD), which frequently persists after therapy even in complete response patients, and extra-medullary disease escape. Positron emission tomography with computed tomography using 18F-deoxyglucose (FDG-PET/CT) is the reference imaging technique for therapeutic assessment and MRD detection in MM. To date, all large prospective cohort studies of transplant-eligible newly diagnosed MM patients have shown a strong and independent pejorative prognostic impact of not obtaining complete metabolic response by FDG-PET/CT after therapy, especially before maintenance. The FDG-PET/CT and MRD (evaluated by flow cytometry or next-generation sequencing at 10-5 and 10-6 levels, respectively) results are complementary for MRD detection outside and inside the bone marrow. For patients with at least a complete response, to reach double negativity (FDG-PET/CT and MRD) is a predictive surrogate for patient outcome. Homogenization of FDG-PET/CT interpretation after therapy, especially clarification of complete metabolic response definition, is currently underway. FDG-PET/CT does not allow MRD to be evaluated when it is negative at initial workup of symptomatic MM. New PET tracers such as CXCR4 ligands have shown high diagnostic value and could replace FDG in this setting. New sensitive functional magnetic resonance imaging (MRI) techniques such as diffusion-weighted MRI appear to be complementary to FDG-PET/CT for imaging MRD detection. The goal of this review is to examine the feasibility of functional imaging, especially FDG-PET/CT, for therapeutic assessment and MRD detection in MM.

| S-EPMC7432032 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data