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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.
JAMA Oncology
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.
International Journal of Molecular Sciences
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.
International Journal of Hematologic Oncology
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.
International Clinical Cytometry Society
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.
Hematology/Oncology Clinics of North America
We review the data supporting MRD testing as well as its limitations and how it may fit in with current and future clinical practice.
Hematology
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.
HemaSphere
These data highlight the value of MRD-driven immune-intervention to induce prompt MRD clearance in the therapy of CLL.
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.
Haematologica
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.
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.
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.
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.
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.
Frontiers in Oncology
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).
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."
Clinical Lymphoma, Myeloma and Leukemia
"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."
Clinical Cancer Research
"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."
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."
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.
Clinical Advances in Hematology & Oncology