The Measurable Residual Disease (MRD) Testing Resource Library connects you to curated materials to help establish and implement MRD testing for your patients with B-cell acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), and multiple myeloma (MM). Search by topic, keyword, target audience (clinical care team, patients, or pediatric population), or by the four sections of the Measurable Residual Disease (MRD) Testing Implementation Roadmap.
Leukemia
In CLL the level of MRD after therapy is an independent predictor of outcome…A parallel analysis of high-throughput sequencing using the ClonoSEQ assay showed good concordance with flow cytometry results at the 0.010% (10(-4)) level, the MRD threshold defined in the 2008 International Workshop on CLL guidelines, but it also provides good linearity to a detection limit of 1 in a million (10(-6)). The combination of both technologies would permit a highly sensitive approach to MRD detection while providing a reproducible and broadly accessible method to quantify residual disease and optimize treatment in CLL.
Treating Blood Cancers LLS Podcast Series for Professionals
MRD refers to the small number of cancer cells that remain in the body after treatment. In this episode, Gail Roboz, MD, from Weill Cornell Medical College, provides an overview of MRD, including understanding its definition, explains the role advancements in technology have played in detection, and underscores the importance of understanding to what degree this detection can be helpful. Dr. Roboz provides strategies to communicate with patients about the impact of MRD on prognosis, treatment and outcomes and discusses the future of MRD testing in blood cancers.
Treating Blood Cancers LLS Podcast Series for Professionals
Dr. Jeffrey Wolf, from the UCSF Helen Diller Family Comprehensive Cancer Center at the University of California San Francisco, explains what MRD is, how providers can explain the role of MRD to patients, including understanding the tests used, how to counsel patients when there is MRD, where testing is done for patients treated in the community, the way MRD test results will be used in the future, and so much more.
Multiple Myeloma Research Foundation (MMRF)
This online, no-cost CME activity, features presentations on current and evolving MM patient care practices and discussions of how they are likely to evolve over the next 3 to 5 years.
International Clinical Cytometry Society
Residual disease detection following therapy is an important prognostic variable in B‐lymphoblastic leukemia. Most flow cytometric strategies for detecting B cell malignancy utilize CD19 to identify B cells. With growing use of anti‐CD19 targeted therapies, alternative strategies are needed for residual disease detection.
Haematologica
A systematic literature review and meta-analysis were performed to elucidate the clinical significance of minimal residual disease with respect to relapse-free survival and overall survival in precursor B-cell ALL.
The Leukemia and Lymphoma Society (LLS)
This website provides links to all of LLS's resources for patients with ALL.
The Leukemia and Lymphoma Society (LLS)
This booklet provides information for patients and their families about ALL in adults.
Medicine X
Learn about ALL through an interactive, web-based, illustrated story.
Leukemia
The European Study Group on MRD detection in ALL (ESG-MRD-ALL), consisting of 30 MRD-PCR laboratories worldwide, has developed guidelines for the interpretation of real-time quantitative PCR-based MRD data. The application of these guidelines ensures identical interpretation of MRD data between different laboratories of the same MRD-based clinical protocol.
ARUP Consult
ARUP offers MRD testing for ALL and other blood cancers.
Blood
We sought to study the self-reported utilization patterns of MRD assessment in CLL and MM, it's use in determining duration of therapy, and the barriers to it's adoption in practice among U.S. cH/O...These data from a limited sample of cH/O suggest that adoption of MRD testing among US cH/O is low, despite results from recent trials that highlight the importance of the MRD negativity as an important prognostic factor in both CLL and MM. Half of cH/O do not measure MRD at any point while treating MM and CLL and less than a fifth incorporate MRD data to determine duration of therapy. The greatest barrier to MRD assessment is the impression that there is lack of evidence supporting its utility in practice at the present time. Further education among cH/O is warranted regarding MRD assessment in CLL and MM given that MRD-negative status is associated with favorable prognosis and should be incorporated in treatment decision-making based on updated guidelines in both diseases.
JAMA Oncology
Minimal residual disease (MRD) refers to the presence of disease in cases deemed to be in complete remission by conventional pathologic analysis. Assessing the association of MRD status following induction therapy in patients with ALL with relapse and mortality may improve the efficiency of clinical trials and accelerate drug development.
Clinical Advances in Hematology & Oncology
Based on available evidence correlating attainment of MRD negativity with outcomes, MRD assessment has been incorporated into ongoing clinical trials. Analyses will provide additional insight into the correlation between MRD and outcome. This monograph examines the available trial data and provides recommendations on how to incorporate MRD assessment into clinical management.
Blood
Among adults with MRD-positive ALL in hematologic remission after chemotherapy, 78% achieved a complete MRD response with blinatumomab...Complete MRD response after blinatumomab treatment in this population was associated with significantly improved OS.
Blood
In this episode, we will review a study that shows that non-invasive imaging of T cell metabolic activity can detect early graft-versus-host disease after allogeneic hematopoietic stem cell transplantation, learn more about how detailed assessment of measurable residual disease in multiple myeloma can better define outcomes and how treatment resistance arises, and finally, examine the mechanism of action and pharmacokinetics of Ciraparantag, a small molecule being developed to rapidly reverse the effects of anticoagulants.
Blood
In this podcast, we’ll look at research demonstrating that the histone acetyltransferase HBO1 is an essential regulator of hematopoietic stem cell function during adult hematopoiesis. Next, we’ll review a large, combined analysis confirming the prognostic value of MRD assessed with next-generation sequencing in 4 randomized trials evaluating daratumumab-based therapies. We’ll conclude with research demonstrating that ferroptosis, a specific type of regulated cell death, is a key mechanism of cardiomyopathy in sickle cell disease.
The Leukemia and Lymphoma Society (LLS)
This booklet describes health insurance options and resources to help patients and their families who are coping with the financial aspects of cancer care.
The Leukemia and Lymphoma Society (LLS)
This handout provides an overview of cancer molecular profiling and its implications in the treatment of blood cancer.
Amgen
CatALLyst™ is an initiative led by a multidisciplinary committee designed to encourage collaboration and provide the latest educational content.
The Leukemia and Lymphoma Society (LLS)
This website provides links to all of LLS's resources for patients with CLL.
National Cancer Institute
Health Professional Version
RTP Research to Practice
Featuring an interview with Dr Steven Coutre on the following topics: Front-line treatment of CLL (0:00) Recent data with ibrutinib-based regimens as first-line therapy for CLL (5:31) Results of the Phase III ELEVATE-TN study evaluating the efficacy and safety of acalabrutinib with obinutuzumab compared to acalabrutinib alone or obinutuzumab with chlorambucil for treatment-naive CLL (14:22) Case: A man in his late 70s experiences atrial fibrillation after receiving ibrutinib as first-line treatment for CLL (19:08) Case: A woman in her early 60s develops arthralgias after treatment with ibrutinib for CLL (25:08) Case: A man in his early 70s receiving ibrutinib for CLL experiences easy bruising on his forearms (27:28) Results from the CLL14 trial evaluating the addition of venetoclax versus chlorambucil to obinutuzumab for patients with previously untreated CLL and coexisting medical conditions (32:06) Monitoring and management of tumor lysis syndrome (TLS) in patients receiving venetoclax (37:07) Impact of minimal residual disease (MRD) assessment on outcomes for patients with CLL (41:26) Spectrum of adverse events with Bruton tyrosine kinase (BTK) inhibitors for CLL (46:22) CME information and select publications.
U.S. National Library of Medicine
A database of privately and publicly funded clinical studies conducted worldwide.
Frontiers in Oncology
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.
Clinical Advances in Hematology & Oncology
ALL is uniquely amenable to quantification of MRD by multiple techniques. Quantification of MRD with high-sensitivity methods not only facilitates risk stratification, but also is used to determine appropriateness of intensified therapy, such as allogeneic hematopoietic cell transplant, as well as MRD-targeted therapy with blinatumomab.
Blood
To identify complementary markers suitable for further treatment stratification in SR ALL, the study evaluated the predictive value of MRD and prospectively monitored MRD in 196 strictly defined SR ALL patients at up to 9 time points in the first year of treatment by quantitative polymerase chain reaction (PCR).
Blood Advances
We explore the important role of the clinical value of MRD use in the real-world practice in MM. We address new topics in the field of MRDs, including the importance of MRD dynamics and prediction of relapse.
British Journal of Haematology
Deeper methods of assessing for MRD in bone marrow in MM such as multiparameter flow cytometry (MFC) and NGS have been shown to be superior predictors of survival compared to traditional response assessment.1-4 However, MRD as a guide for clinical decision-making remains unproven, likely due to disparate patterns of MRD techniques and usage in clinical trials and clinical care. In light of the many uncertainties regarding MRD as a clinical decision-making tool and surrogate endpoint for clinical trials, we sought to understand contemporary clinician attitudes and practices toward the use and measurement of MRD in MM.
CLL Society
The CLL Society is an inclusive, patient-centric, physician-curated nonprofit organization that addresses the unmet needs of the CLL community through patient education, advocacy, support, and research.
VJHemeOnc The Video Journal of Hematological Oncology
CLL is a disorder characterized by morphologically mature but immunologically less mature lymphocytes, which accumulate in the bone marrow, lymphatic tissue and blood. CLL generally affects the older population and is incurable, however, several novel treatment approaches have developed to improve outcomes of patients with CLL and there is an increasing use of MRD in disease monitoring. In this podcast, Lydia Scarfò, of Vita-Salute San Raffaele University & IRCCS San Raffaele Scientific Institute, Milan, Italy, Othman Al-Sawaf of the University Hospital of Cologne, Cologne, Germany, and Tanya Siddiqi, from City of Hope, Duarte, CA discuss key developments in the treatment of CLL presented at this years EHA meeting.
Blood
MRD is an established and sensitive prognostic tool to assess the depth of response during and after treatment of chronic lymphocytic leukemia CLL and to understand disease dynamics after treatment. Retracing these kinetics is paramount to understand which group of patients is at risk of relapsing despite initial MRD response. To this end, we here provide an analysis of clonal growth patterns in patients treated within the CLL14 trial.
Blood Cancer Journal
Results reinforce the role of MRD detection by different strategies in patient prognosis and highlight the use of MRD as an endpoint for multiple myeloma treatment.
The Leukemia and Lymphoma Society (LLS)
Hacer preguntas a su médico acerca de los ensayos clínicos en cualquier fase de su tratamiento le ayudará a usted y a su doctor a manejar su atención médica de forma más efectiva. Vea estos videos y descargue la guía de conversación a continuación para mejorar la comunicación con su médico con respecto a sus necesidades de atención médica.
New England Journal of Medicine
Lenalidomide plus dexamethasone is a standard treatment for patients with newly diagnosed multiple myeloma who are ineligible for autologous stem-cell transplantation. We sought to determine whether the addition of daratumumab would significantly reduce the risk of disease progression or death in this population.
Blood
Although advances in frontline therapy have yielded unprecedented improvement in long-term patient outcomes, surrogate markers of PFS and OS are needed. In this regard, achievement of stringent complete response (CR; sCR) after ASCT is associated with improvement in median PFS and OS.8,9 Similarly, minimal residual disease (MRD) testing has emerged as a sensitive measure of depth of response that strongly correlates with PFS and OS.
Blood
The persistence of MRD during therapy is the strongest adverse prognostic factor in ALL. We developed a high-throughput sequencing method that universally amplifies antigen-receptor gene segments and identifies all clonal gene rearrangements (i.e., leukemia-specific sequences) at diagnosis, allowing monitoring of disease progression and clonal evolution during therapy.
Blood Reviews
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.
VJHemeOnc The Video Journal of Hematological Oncology
Nitin Jain, MD, of the University of Texas MD Anderson Cancer Center, Houston, TX, and Anthony Mato, MD, and Meghan Thompson, MD, both from Memorial Sloan Kettering Cancer Center, New York, NY, discuss some of the latest updates in CLL treatment presented at this year’s virtual American Society of Hematology (ASH) meeting.
Cancer
In adults with relapsed/refractory ALL receiving first salvage therapy, achievement of MRD negativity is an important therapeutic outcome. Patients who achieve MRD negativity with first salvage treatment and undergo SCT have the best long-term survival.
CURE
Experts discuss CLL information highly relevant to patients, caregivers and advocates right now.
Haematologica
These data highlight the value of MRD-driven immune-intervention to induce prompt MRD clearance in the therapy of CLL.
VJHemeOnc The Video Journal of Hematological Oncology
Bruno Paiva, PhD, of the University of Navarra, Pamplona, Spain, Noemi Puig, MD, PhD, of the University Hospital Salamanca, Salamanca, Spain, and Benjamin Derman, MD, of the University of Chicago, Chicago, IL, discuss key research, presented at this year’s Congress of the European Hematology Association (EHA 2021), investigating the role of MRD in the management of multiple myeloma.
Agency for Healthcare Research and Quality (AHRQ)
This websites provides key elements of an evaluation plan, which can help guide your evaluation efforts.
Leukemia
Here, the EuroClonality (BIOMED-2) consortium summarizes important pre- and post-analytical aspects of clonality testing, provides guidelines for interpretation of clonality testing results, and presents a uniform way to report the results of the Ig/TCR assays.
Therapeutic Advances in Hematology
Studies have demonstrated that achievement of MRD negativity after induction chemotherapy or during consolidation is associated with significantly better long-term outcomes, and MRD status constitutes an independently prognostic marker, often superseding other conventional risk factors.
Journal of Clinical Oncology
In relapsed and/or refractory multiple myeloma, daratumumab reduced the risk of progression or death by > 60% in POLLUX (daratumumab/lenalidomide/dexamethasone [D-Rd]) and CASTOR (daratumumab/bortezomib/dexamethasone [D-Vd]). Minimal residual disease (MRD) is a sensitive measure of disease control. Sustained MRD negativity and outcomes were evaluated in these studies.
Journal of Hematology & Oncology
This comprehensive review focuses on the recent advances and future directions in novel therapeutic strategies in adult ALL.
Amgen
The following is a list of facilities that are CLIA-certified and accept external MRD samples. Amgen neither recommends nor endorses, and may or may not have financial relationships with, any facility that appears on this list. This list is not intended to be a comprehensive list nor as a referral to any provider listed. If you would like to suggest a facility to be added to this list, please contact Amgen MedInfo at 800-77-AMGEN.
The Leukemia and Lymphoma Society (LLS)
This Fact Sheet for healthcare professionals will explain the methods currently used for MRD assessment, how and when testing should occur for different hematologic malignancies, and how the resulting information can inform prognosis and decisions about care.
Association of Community Cancer Centers (ACCC)
The Financial Advocacy Network's tools and resources empower providers to proactively integrate financial health into the oncology care continuum and help patients gain access to high-quality care for a better quality of life.
Journal of Clinical Oncology
The MURANO study demonstrated significant progression-free survival benefit for fixed-duration venetoclax-rituximab compared with bendamustine-rituximab in relapsed/refractory chronic lymphocytic leukemia. With all patients off treatment, we report MRD kinetics and updated outcomes.
Leukemia
In a multicenter study, MRD was measured prospectively on 598 follow-up bone marrow samples from 102 high-risk children and 136 adult ALL patients, using IG/TCR-QPCR and 4/5 color MFC.
Nature Medicine
Authors identified genetic mutations in CD19 and loss of heterozygosity at the time of CD19– relapse to chimeric antigen receptor (CAR) therapy.
Amgen
In both children and adults with ALL, MRD testing as early as induction therapy has been shown to have prognostic significance.
The Leukemia and Lymphoma Society (LLS)
This palm card provides an overview of financial assistance programs offered by LLS.
Blood
BCR-ABL1–positive cells outside the B-lineage compartment are found in 40% of adult patients with BCR-ABL1–positive BCP-ALL. Selection of preexisting CD19– subclones is a potential source of tumor escape after CD19-targeted therapies in adult Philadelphia chromosome–positive ALL.
Multiple Myeloma Research Foundation (MMRF)
A short video explaining what MRD is and how testing for MRD may be used for people with multiple myeloma.
Biological Sciences
The primary cause of poor outcome following allogeneic HCT for CLL is disease recurrence. Detection of increasing MRD following HCT may permit early intervention to prevent clinical relapse; however, MRD quantification remains an uncommon diagnostic test because of logistical and financial barriers to widespread use. Here we describe a method for quantifying CLL MRD using widely available consensus primers for amplification of all Ig heavy chain (IGH) genes in a mixture of peripheral blood mononuclear cells, followed by high-throughput sequencing for disease-specific IGH sequence quantification.
American Journal of Clinical Pathology
This article presents an approach to MRD detection in B-LL/L by flow cytometry through case presentations with illustration of several potential pitfalls.
American Society of Hematology (ASH)
Of all the hematologic malignancies, multiple myeloma has one of the greatest disparities in incidence and prevalence, with incidence in African American patients more than twice that in white patients. These podcasts will teach clinicians culturally sensitive approaches for management of multiple myeloma in African Americans, how to address barriers due to racial disparities, and strategies to implement newly gained knowledge for the best outcomes of African American patients with multiple myeloma.
Leukemia
Detection of MRD in CLL is becoming increasingly important as treatments improve...There was good correlation between four-CLR and six-CLR panels in dilution studies and clinical samples, with 100% concordance for detection of residual disease at the 0.01% (10−4) level (n=59) and good linearity even at the 0.001–0.01% (10−5–10−4) level. A six-CLR panel therefore provides equivalent results to the four-CLR panel but it requires fewer reagents, fewer cells and a much simpler analysis approach.
VJHemeOnc The Video Journal of Hematological Oncology
Natalie Callander, MD, of the University of Wisconsin School of Medicine and Public Health, Madison, WI, Luciano Costa, MD, PhD, of the UAB School of Medicine, Birmingham, AL, Fredrik Schjesvold, MD, PhD, of the Oslo Myeloma Center Oslo University, Oslo, Norway, Lanny Kirsch, MD, Senior Vice President in Translational Medicine at Adaptive Biotechnologies, Seattle, WA, and Philippe Moreau, MD, of the Nantes University Hospital, Nantes, France, discuss the latest data on the use of MRD in the management and treatment of multiple myeloma, as presented at the 18th International Myeloma Workshop (IMW 2021).
Journal of Clinical Oncology
The ASCO Expert Panel determined that the recommendations from the guideline, published in 2016, are clear, thorough, and based on the most relevant scientific evidence. ASCO fully endorsed the CAP-ASH guideline on initial diagnostic work-up of acute leukemia and included some discussion points according to clinical practice and updated literature.
Archives of Pathology & Laboratory Medicine
The guideline provides a framework for the multiple steps, including laboratory testing, in the evaluation of acute leukemia samples. Some aspects of the guideline, especially molecular genetic testing in acute leukemia, are rapidly changing with new supportive literature, which will require on-going updates for the guideline to remain relevant.
Leukemia
Minimal residual disease (MRD) assessment is incorporated in an increasing number of multiple myeloma (MM) clinical trials as a correlative analysis, an endpoint or even as a determinant of subsequent therapy. There is substantial heterogeneity across clinical trials in how MRD is assessed and reported, creating challenges for data interpretation and for the design of subsequent studies. We convened an international panel of MM investigators to harmonize how MRD should be assessed and reported in MM clinical trials. The panel provides consensus on which MM trials should include MRD, the recommended time points for MRD assessment, and expected analytical validation for MRD assays.
International Myeloma Foundation (IMF)
"From doctors to patients, the goal of these publications is to help anyone better understand aspects of myeloma. The information provided in the International Myeloma Working Group’s publications seeks to help guide patients and their doctors to treating myeloma in the most effective way for every individual case."
The Lancet Oncology
The International Myeloma Working Group has defined new response categories of minimal residual disease negativity, with or without imaging-based absence of extramedullary disease, to allow uniform reporting within and outside clinical trials. In this Review, we clarify several aspects of disease response assessment, along with endpoints for clinical trials, and highlight future directions for disease response assessments.
Blood
Recent advances including the discovery of the genomic landscape of the disease, the development of genetic tests with prognostic relevance, and the detection of minimal residual disease (MRD), coupled with the increased availability of novel targeted agents with impressive efficacy, prompted an international panel to provide updated evidence- and expert opinion–based recommendations. These recommendations include a revised version of the iwCLL response criteria, an update on the use of MRD status for clinical evaluation, and recommendations regarding the assessment and prophylaxis of viral diseases during management of CLL.
Multiple Myeloma Research Foundation (MMRF)
Our faculty will review the importance of MRD for multiple myeloma patients and strategies to reach and stay MRD negative. This webinar will provide timely information to keep patients and caregivers up to date on the important progress being made in myeloma today, help them communicate more effectively with their health care team, and empower them to achieve the best possible outcome for their disease.
Blood
Ten of 36 patients (28%) achieved an OS ≥30 months in a blinatumomab study in relapsed/refractory acute lymphoblastic leukemia. Long-term survival may be associated with T-cell expansion, B-cell depletion, and a minimal residual disease response.
Journal of Hematology & Oncology
In this retrospective study, we present the results from a multinational and multicenter series of 400 patients with MRD monitoring during front-line therapy with the aim of exploring how clinical decisions made based on those MRD results affected outcomes...Herein, we find that MRD is useful in guiding clinical decisions during initial therapy and has a positive impact on PFS in MM patients. This potentially opens a new dimension for the use of MRD in MM, but this role still remains to be confirmed in prospective, randomized clinical trials.
The Leukemia and Lymphoma Society (LLS)
This website offers tips, worksheets, and other resources to help patients stay organized and manage insurance and costs during illness.
Journal of Hematology & Oncology
Assessment of MRD is rapidly transforming the therapeutic and prognostic landscape of a wide range of hematological malignancies. Its prognostic value in ALL has been established and MRD measured at the end of induction is increasingly used to guide further therapy. Although MRD detectable immediately before allogeneic HCT is known to be associated with poor outcomes, it is unclear if or to what extent this differs with different types of conditioning.
Journal of Clinical Oncology
Assessing measurable residual disease (MRD) has become standard with many tumors, but the clinical meaning of MRD in multiple myeloma (MM) remains uncertain, particularly when assessed by next-generation flow (NGF) cytometry. Thus, we aimed to determine the applicability and sensitivity of the flow MRD-negative criterion defined by the International Myeloma Working Group (IMWG).
Leukemia
This review article presents "the work of an international, multidisciplinary, 174-member panel convened to identify critical questions on key issues pertaining to MRD in chronic lymphocytic leukemia, review evaluable data, develop unified answers in conjunction with local expert input, and provide recommendations for future studies. Recommendations are presented regarding methodology for MRD determination, assay requirements and in which tissue to assess MRD, timing and frequency of assessment, use of MRD in clinical practice versus clinical trials, and the future usefulness of MRD assessment.
Leukemia & Lymphoma
This review aims to critically analyze the key MRD aspects including the current evidence supporting the use of MRD in clinical practice and the pitfalls of the various methods used to assess MRD. The utility of MRD for light chain (AL) amyloidosis will also be discussed.
Journal of Hematology & Oncology
The landscape of multiple myeloma has changed considerably in the past two decades regarding new treatments, insight into disease biology and innovation in the techniques available to assess MRD as the most accurate method to evaluate treatment efficacy. The sensitivity and standardization achieved by these techniques together with unprecedented rates of CR induced by new regimens, raised enormous interest in MRD as a surrogate biomarker of patients’ outcome and endpoint in clinical trials. By contrast, there is reluctance and general lack of consensus on how to use MRD outside clinical trials. Here, we discuss critical aspects related with the implementation of MRD in clinical practice.
American Society of Hematology (ASH)
Malignant hematology is famous for its three-letter acronyms: MDS, CML, ALL, CLL, and the list goes on. The newest and most talked-about kid on the block is MRD, or measurable residual disease (previously known as minimal residual disease). Indeed, the term MRD has become so ubiquitous that it has elbowed out its older MRD cousin from the transplant world (“matched related donor,” now often referred to as a sibling donor). If you’re like us though, you have likely heard about MRD only from conferences or in clinic. As part of a new series for ASH TraineE-News, we will review these sorts of learned-on-the-fly concepts in more detail. Our first topic? You guessed it, MRD!
Clinical Lymphoma, Myeloma and Leukemia
"Patients with CLL who achieve undetectable MRD (U-MRD) (ie, < 10-4 detectable leukemic cells in peripheral blood or bone marrow) have better outcomes than those with detectable MRD. To assess the magnitude of improvement of PFS or OS in patients who achieved U-MRD after upfront chemotherapy (CT) or chemo-immunotherapy (CIT), we conducted a systematic review and meta-analysis...U-MRD status after treatment with CT or CIT in newly diagnosed CLL is associated with long-term survival. These findings provide quantitative evidence to support the integration of MRD assessment as an end point in clinical trials of CLL."
Journal of Clinical Oncology
MRD quantification allows for improved PFS prediction in both patients who achieve PR and CR, which thus supports its application in all responders. In contrast to residual lymphadenopathy, persisting splenomegaly does not impact outcome in patients with MRD-negative PR.
HemaSphere
This review outlines current methods of MRD detection in CLL and summarizes MRD data from relevant trials. The significance of MRD testing in clinical studies and in routine patient care is assessed and new MRD-guided treatment strategies are discussed.
Frontiers in Oncology
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.
International Journal of Molecular Sciences
Current methods to diagnose MRD are through phenotypic marker patterns or differential gene patterns through analysis by flow cytometry, polymerase chain reaction, real-time quantitative polymerase chain reaction, reverse transcription polymerase chain reaction or NGS.
Blood
MRD diagnostics has proven to be the strongest prognostic factor, allowing for risk group assignment into different treatment arms, ranging from significant treatment reduction to mild or strong intensification. Also in relapsed ALL patients and patients undergoing stem cell transplantation, MRD diagnostics is guiding treatment decisions.
Frontiers in Oncology
Through a review of the literature and in house data, authors analyze the current status of MRD assessment in ALL to better understand how some of its limitations could be overcome by emerging molecular technologies. Authors highlight the future role of MRD monitoring in the context of personalized protocols, taking into account the genetic complexity in ALL.
Blood
Early response to therapy is one of the most important prognostic factors in acute leukemia, which prompted authors to investigate whether or not early immunophenotypic assessment of MRD could also be a valuable tool for predicting relapse in adult patients with ALL. For that purpose, this study analyzed the level of MRD during the initial phase of treatment (induction phase) by multiparameter flow cytometry in a series of 102 adolescent (older than 14 years) and adult patients with ALL.
Frontiers in Oncology
This review discusses the standardized and innovative technical approaches for MRD detection in CLL, the clinical impact of MRD monitoring in chemoimmunotherapy and chemo-free trials and the future clinical implications of MRD monitoring in CLL patients outside of clinical trials.
Journal of the Advanced Practitioner in Oncology
Advanced practitioners should be cognizant of how MRD is defined, measured, and may be applied to therapeutic decision-making in the clinical management of CLL. This brief summary from the 2020 Society of Hematological Oncology (SOHO) meeting covers MRD methods, data, and considerations for advanced practice providers.
International Journal of Hematologic Oncology
Brief review article that concludes, "With the approval of several new drugs with different mechanisms of action and the incorporation of MRD as an end-point in clinical trials, the management landscape of MM is changing rapidly. Given the significant impact of MRD negativity on the outcomes, it could be a new regulatory surrogate end-point for survival in clinical trials and a main driver of research and clinical practice in MM in the future.
Nature reviews. Clinical oncology.
This Review presents an overview of the various techniques for MRD detection in patients with MM. In addition, this article discusses challenges and opportunities for the routine use of MRD testing, possible future directions for clinical trials and implications for drug approval processes.
Frontiers in Oncology
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.
Biomarker Research
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.
Hematology
We review the data supporting MRD testing as well as its limitations and how it may fit in with current and future clinical practice.
Clinical Cancer Research
"Given all the progress, it is not surprising that a number of clinicians are now considering using MRD to inform real-world clinical care of patients across the spectrum from smoldering myeloma to relapsed refractory multiple myeloma, with each disease setting presenting key challenges and questions that will need to be addressed through clinical trials. The pace of advances in targeted and immune therapies in multiple myeloma is unprecedented, and novel MRD-driven biomarker strategies are essential to accelerate innovative clinical trials leading to regulatory approval of novel treatments and continued improvement in patient outcomes."
Blood
Patients who were MRD negative had a higher probability of prolonged progression-free survival than patients with detectable residual disease, regardless of treatment group (RVD vs transplant), cytogenetic risk profile, or International Staging System disease stage at diagnosis. These results were similar after completion of maintenance therapy. Our findings confirm the value of MRD status, as determined by NGS, as a prognostic biomarker in multiple myeloma, and suggest that this approach could be used to adapt treatment strategies in future clinical trials.
Clinical Lymphoma, Myeloma and Leukemia
Therapeutic advances have greatly extended survival times in patients with multiple myeloma, necessitating increasingly lengthy trials when using survival outcomes primary endpoints. A surrogate endpoint that can more rapidly predict survival could accelerate drug development. We conducted a meta-analysis to evaluate minimal residual disease (MRD) status as a valid PFS surrogate in newly diagnosed multiple myeloma (NDMM).
Cancer Care Ontario
These guidelines provide evidence surrounding the clinical utility of MRD testing using multiparameter flow cytometry (MFC), next-generation sequencing (NGS), or polymerase chain reaction (PCR)-based methods in patients with ALL.
The Leukemia and Lymphoma Society (LLS)
This handout provides an overview of MRD for individuals with blood cancer.
Multiple Myeloma Research Foundation (MMRF)
MMRF has a collection of valuable resources to support people living with multiple myeloma and their loved ones. Get expert insights from our Patient Navigation Center, find emotional and financial support, and stay informed with our educational programs.
Multiple Myeloma Research Foundation (MMRF)
The toolkit includes the following educational resource booklets: Multiple Myeloma Disease Overview, Multiple Myeloma Treatment Overview, Managing My Myeloma, Multiple Myeloma Caregiver Guide and The Path to Precision Medicine. The toolkit is available in English and Spanish and can be downloaded or order a copy through the mail.
Blood
Although levels of minimal residual disease (MRD) decrease below the detection limit in most adult patients with standard-risk ALL after consolidation treatment, about 30% of these patients will ultimately relapse. To evaluate the power of MRD monitoring as an indicator of impending relapse, we prospectively analyzed postconsolidation samples of 105 patients enrolled in the GMALL trial by real-time quantitative polymerase chain reaction (PCR) of clonal immune gene rearrangements.
Association of Community Cancer Centers (ACCC)
This webinar provides the multidisciplinary cancer team with important and practical information for the assessment of MRD as part of routine clinical practice for their patients with CLL. The presentation will be valuable for understanding the impact of MRD on treatment decisions and practice patterns, which has promise to lead to major improvements in outcomes for CLL patients in the very near future.
Multiple Myeloma Center for Nurses
Find answers to some of the most commonly asked questions about multiple myeloma from nurses and patients.
The Leukemia and Lymphoma Society (LLS)
This website provides links to all of LLS's resources for patients with myeloma.
National Comprehensive Cancer Network (NCCN)
NCCN offers clinical guidelines to guide the treatment and care of patients with ALL. (Create a free account profile to access guidelines.)
National Comprehensive Cancer Network (NCCN)
NCCN offers clinical guidelines to guide the treatment and care of patients with CLL. (Create a free account profile to access guidelines.)
National Comprehensive Cancer Network (NCCN)
NCCN offers clinical guidelines to guide the treatment and care of patients with multiple myeloma. (Create a free account profile to access guidelines.)
Leukemia Stem Cells: Methods and Protocols
Next-generation sequencing (NGS) of immunoglobulin (IG) and T cell receptor (TR) rearrangements represents a modern alternative to classical RQ-PCR-based MRD detection.
Hematologic Oncology Update
Featuring discussions on the role of minimal residual disease evaluation in the management of multiple myeloma and chronic lymphocytic leukemia with Drs Shaji Kumar and Philip Thompson, moderated by Dr Neil Love.
The Leukemia and Lymphoma Society (LLS)
Download or order free information booklets from LLS.
Lancet
Standard-of-care treatment for patients with newly diagnosed multiple myeloma includes combination therapies for patients who are not eligible for autologous stem-cell transplantation. At the primary analysis for progression-free survival of the phase 3 ALCYONE trial, progression-free survival was significantly longer with daratumumab in combination with bortezomib, melphalan, and prednisone (D-VMP) versus bortezomib, melphalan, and prednisone (VMP) alone in patients with transplant-ineligible, newly diagnosed multiple myeloma. Here we report updated efficacy and safety results from a prespecified, interim, overall survival analysis of ALCYONE with more than 36 months of follow-up.
Association of Community Cancer Centers (ACCC)
Find the most up-to-date information on oncology assistance and reimbursement programs by searching for a prescribed product or company name, then further streamline your search by applying coverage and assistance-type filters. Access details on all available financial assistance and reimbursement program benefits, application information, and eligibility criteria. Listings include direct links to external websites and company phone numbers and will be updated in real-time, so you’ll always have access to the latest information and external program links. The digital Guide links directly to the ICD-10 codes website and the Library of NCCN Compendia for current indications. These resources were identified by ACCC members as the most up-to-date and authoritative source for this information.
The Leukemia and Lymphoma Society (LLS)
A complete list of LLS's financial assistance programs to help individuals with blood cancer. You can also call 877-557-2672 to reach LLS's Patient Financial Assistance Programs.
Mountain-Pacific Quality Health
This worksheet can help you develop and guide your PDSA cycle.
The Leukemia and Lymphoma Society (LLS)
This video series aims to answer many questions that patients may have about lab and imaging tests.
The Leukemia and Lymphoma Society (LLS)
This palm card provides a list of support services offered by LLS.
National Cancer Institute
Health Professional Version
Leukemia
PCR assessment of clonal T-cell receptor (TCR) and immunoglobulin (Ig) gene rearrangements is an important diagnostic tool in mature T-cell neoplasms...Our study indicates that the BIOMED-2 multiplex PCR tubes provide a powerful strategy for clonality assessment in T-cell malignancies assisting the firm diagnosis of T-cell neoplasms.
American Society of Hematology (ASH)
The series is designed to provide clinicians and researchers in hematology foundational information on the latest technologies available [including MRD] for data acquisition, diagnosis, and decision making for hematologic diseases.
Blood
Initial imatinib-based therapy of Ph+ adult ALL is associated with lower early mortality and higher CR rate. In adults with Ph+ ALL, allogeneic SCT in first CR prolongs relapse-free survival and OS.
PLoS One
Due to small sample size, adjusted models could not be constructed for sCR or MRD. Nevertheless, evidence of significant survival benefit (p<0.05) associated with MRD negativity and sCR was identified across real-world studies. These findings provide support for the use of response outcomes as surrogate endpoints to estimate PFS benefit in NDMM.
Blood
This article shows that poor early MRD response, in contrast to conventional ALL risk factors, is an excellent tool to identify patients who may benefit from allogeneic SCT in the context of intensified adult ALL therapy.
Journal of Clinical Medicine
Brief review of imaging-based sensitive response assessment through the use of functional rather than morphological whole-body imaging techniques, such as positron emission tomography with computed tomography and magnetic resonance imaging, as a strategy to overcome limitations of flow-cytometry or molecular-based methods, such as the patchy infiltration of bone marrow plasma cells and the presence of extra-medullary, in evaluating response to therapy and in the assessment of the MRD status in MM patients.
The Lancet Oncology
Adults with relapsed or refractory B-precursor acute lymphoblastic leukaemia have an unfavourable prognosis…This study aimed to confirm the activity and safety profile of blinatumomab for ALL.
Leukemia
Achieving undetectable MRD status after chemoimmunotherapy predicts longer progression-free and overall survival. The predictive factors and timing of relapse in patients with U-MRD and value of interim MRD analysis are ill-defined. This was a prospective study of 289 patients with CLL treated first-line with FCR. MRD analysis was performed after course 3 (C3) and at end-of-therapy (EOT) in bone marrow...Interim MRD status may be used for risk stratification and to individualize therapy... which may allow development of early intervention strategies.
Hematology/Oncology Clinics of North America
This review discusses available methods of minimal residual disease measurement. It summarizes minimal residual disease data from pivotal clinical trials and discusses potential implications for future studies and minimal residual disease-based clinical strategies.
Leukemia
Polymerase chain reaction (PCR) assessment of clonal immunoglobulin (Ig) and T-cell receptor (TCR) gene rearrangements is an important diagnostic tool in mature B-cell neoplasms...Our study indicates that the BIOMED-2 multiplex PCR assays provide a powerful strategy for clonality assessment in B-cell malignancies resulting in high Ig clonality detection rates particularly when IGH and IGK strategies are combined.
Blood
A fully-standardized EuroFlow 8–color antibody panel and laboratory procedure was stepwise designed to measure MRD in B-cell precursor ALL patients with a sensitivity of ≤10−5, comparable to real-time quantitative polymerase chain reaction (RQ-PCR)–based MRD detection via antigen-receptor rearrangements.
Leukemia
Amplicon-based next-generation sequencing (NGS) of immunoglobulin (IG) and T-cell receptor (TR) gene rearrangements for clonality assessment, marker identification and quantification of minimal residual disease (MRD) in lymphoid neoplasms has been the focus of intense research, development and application. However, standardization and validation in a scientifically controlled multicentre setting is still lacking.
British Journal of Hematology
This study prospectively evaluated the significance of MRD. Patients were treated with a uniform Polish Adult Leukemia Group 4‐2002 protocol. MRD status was assessed after induction and consolidation by multiparametric flow cytometry.
The Leukemia and Lymphoma Society (LLS)
This website provides a list and links to all of LLS's support resources.
Blood
In patients with transplant-ineligible newly diagnosed multiple myeloma (NDMM), daratumumab reduced the risk of disease progression or death by 44% in MAIA (daratumumab/lenalidomide/dexamethasone [D-Rd]) and 58% in ALCYONE (daratumumab/bortezomib/melphalan/prednisone [D-VMP]). Minimal residual disease (MRD) is a sensitive measure of disease and response to therapy. MRD-negativity status and durability were assessed in MAIA and ALCYONE.
The Leukemia and Lymphoma Society (LLS)
This three minute video provides an overview of MRD and MRD testing options.
The Leukemia and Lymphoma Society (LLS)
This booklet provides information for patients and their families about ALL.
PLoS One
Our results confirm that sCR does not predict a different outcome and indicate that more sensitive techniques are able to identify patients with differing prognoses. We suggest that MRD categories should be implemented over sCR for the future classification of MM responses.
VJHemeOnc The Video Journal of Hematological Oncology
John Gribben of Barts Cancer Institute, London, UK, chairs an insightful discussion with Barbara Eichhorst of the University of Cologne, Cologne, Germany, Susan O’Brien of the University of California, Irvine, CA, and Matthew Davids of Dana-Farber Cancer Institute, Boston, MA, on the latest CLL updates from the recent Virtual ASCO and EHA 2020 Meetings. The speakers discuss frontline therapy for CLL, BTK inhibitors, novel combination therapies and the importance of measurable residual disease (MRD) assessment. Treatment sequencing and novel therapies, in particular CAR T-cell approaches were also discussed.
Clinical Advances in Hematology & Oncology
"This monograph examines clinical trial data regarding the role of MRD in CLL, and provides recommendations on how to incorporate MRD assessment into clinical management."
The Leukemia and Lymphoma Society (LLS)
This webcast provides an overview of treatment options for patients living with ALL, MRD testing, clinical trials, and the importance of open communication with the healthcare team.
The Leukemia and Lymphoma Society (LLS)
Dedicated to curing leukemia, lymphoma, myeloma, and other blood cancers, The Leukemia & Lymphoma Society (LLS), the world's largest voluntary (nonprofit) health organization dedicated to funding blood cancer research and providing education and patient services.
The Leukemia and Lymphoma Society (LLS)
By completing this form, your patient will be contacted by a LLS Information Specialist. Information Specialists are social workers, nurses and health educators with expertise in blood cancers who provide personalized support to patients, caregivers, and families.
The Multiple Myeloma Research Foundation (MMRF)
The Multiple Myeloma Research Foundation (MMRF) drives discoveries for new treatments, accelerates groundbreaking clinical trials and fuels the most robust data-driven initiatives in cancer research. Our goal is to find a cure for each and every patient diagnosed with multiple myeloma.
Association of Community Cancer Centers (ACCC)
Drs. Rafael Fonseca and Tara Graff—discuss the benefits of MRD testing for patients with Multiple Myeloma and CLL, the importance of training the multidisciplinary care team, and the promise of MRD testing to improve patient outcomes as its adoption continues to grow.
Clinical Advances in Hematology & Oncology
"In this review, we summarize currently available methods of MRD detection, provide recent MRD data and outcomes from clinical trials in CLL, and discuss open questions and future approaches for MRD within and outside clinical trials."
American Society for Transplantation and Cellular Therapy (ASTCT) Talks
In this podcast, we chat with industry leaders from all areas of the blood and marrow transplantation and cellular therapy field, including doctors, physician assistants, pharmacists, nurses, administrators, social workers, and more.
Journal of Clinical Oncology
In previous analyses of the MURANO study, fixed-duration venetoclax plus rituximab (VenR) resulted in improved progression-free survival compared with bendamustine plus rituximab (BR) in patients with relapsed or refractory CLL. At the 4-year follow-up, we report long-term outcomes, response to subsequent therapies, and the predictive value of molecular and genetic characteristics.