What gets measured gets managed®
WHAT IS MRD?
Measurable Residual Disease
Measurable (or minimal) residual disease (MRD) refers to the small number of cancer cells that can remain in a patient’s body during and after treatment and may eventually cause recurrence of the disease. These residual cells typically cause no physical signs or symptoms and are present at such low levels that more refined and sensitive techniques are required to identify them.
Monitoring MRD at various points throughout the course of treatment and remission provides important insight into the status of a patient’s disease in lymphoid malignancies like chronic lymphocytic leukemia, multiple myeloma, and acute lymphoblastic leukemia.[1-6]
HOW IS MRD MEASURED?
Advanced technologies are improving clinicians’ ability to confidently monitor MRD
CONVENTIONAL DETECTION
Clinicians have been evaluating residual disease in lymphoid cancers for decades, but historically, MRD assessment lacked the precision and sensitivity to identify and track disease at the low levels where disease often lurks.[7]
Among conventional MRD detection methods, no single test offered the deepest levels of sensitivity, an accurate quantification of disease burden, and the standardization necessary to provide clinicians with confidence in the results.[7]
ENHANCED DETECTION
Recent advancements in MRD testing, driven by development of the clonoSEQ® Assay, have enabled precise identification and quantitation of the specific DNA sequences associated with lymphoid malignancy, empowering clinicians to accurately and reliably assess a patient’s MRD status at any point during treatment or remission.[8-10]
WHY MEASURE MRD?
Accurate MRD assessment can guide clinicians in developing personalized treatment approaches
The enhanced ability to monitor MRD has the potential to inform patient management decisions in several important ways:
MRD assessment can help predict clinical outcomes
Given the nature of current therapies, some patients will achieve remission of their disease while others ultimately relapse.[9] The goal of utilizing MRD in patient management is to be able to detect residual disease at the lowest level possible in order to be confident in a patient’s MRD status. Data demonstrates that deep MRD negativity correlates with improved outcomes. As a result, clinicians can use MRD test results to assess a patient’s response to treatment, which may inform decisions made throughout the treatment continuum.[8]
MRD enables for early detection of relapse
Quantitative MRD assessment may identify progression of disease much sooner than the onset of physical signs and symptoms. The more sensitive the MRD detection assay, the sooner impending relapse can be identified.[9] This “lead time” gained by not waiting until physical signs and symptoms emerge may allow a clinician to intervene earlier to regain control of a patient’s disease.[11]
Deep sensitivity enables early detection of relapse, allowing for possible early intervention.[11]
THE FUTURE OF MRD
MRD is emerging as a key measure of efficacy for new therapies
Drug developers are increasingly leveraging MRD assessment to expedite the approval of innovative therapeutics.[12] The prognostic value of MRD assessment has been demonstrated in multiple diseases, and measurement of residual disease is currently being evaluated as a way to measure efficacy in drug trials, with the potential to expedite the approval of emerging therapies.[8,13]
To date, much of this research has been performed using different assays with varying levels of sensitivity and inconsistent approaches, which has limited the ability to broadly standardize MRD assessment.[7]
For results to be considered reliable and broadly applicable, an MRD assay needs to be:
Highly Senstive
Widely Available
Compliant with Regulatory Requirements
Reproducible Using Standardized Methods
Capable of Meeting the High Bar for Incorporation in Clinical Trials
Investigators studying multiple hematologic malignancies have found that the clonoSEQ Assay meets these strict requirements and they are turning to clonoSEQ as a standardized approach for MRD detection in clinical trials around the world.[14]
This page is intended for use by healthcare professionals outside of the United States.
The clonoSEQ Assay B-cell Reagent Set is an in vitro diagnostic that identifies and quantifies rearranged B-cell receptor gene sequences in DNA extracted from blood and bone marrow.
It is a manual test that determines measurable/minimal residual disease (MRD) and monitors changes in disease burden during and after treatment in B-cell malignancies. The test is indicated for use by qualified healthcare professionals for clinical decision-making and in conjunction with other clinicopathological features.
The clonoSEQ Assay is being utilized for a variety of investigator-sponsored clinical trials in B-cell lymphoid cancers. If you are interested in learning more about use of clonoSEQ in your own trials, contact dxsupport@adaptivebiotech.com.
Citations
- Wu D, et al. Clin Cancer Res. 2014;20(17):4540-8.
- Korde N, et al. JAMA Oncol. 2015;1(6):746-54.
- Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Pediatric Acute Lymphoblastic Leukemia V.2.2020. © National Comprehensive Cancer Network, Inc. 2020. All rights reserved. Accessed March 11th, 2020. To view the most recent and complete version of the guideline, go to NCCN.org.
- Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Acute Lymphoblastic Leukemia V.1.2020. © National Comprehensive Cancer Network, Inc. 2020. All rights reserved. Accessed March 11th, 2020. To view the most recent and complete version of the guideline, go to NCCN.org.
- Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Multiple Myeloma V.3.2020. © National Comprehensive Cancer Network, Inc. 2020. All rights reserved. Accessed March 11th, 2020. To view the most recent and complete version of the guideline, go to NCCN.org.
- Sherrod AM, et al. Bone Marrow Transplant. 2015;51:2-12.
- clonoSEQ®. [technical summary]. Seattle, WA: Adaptive Biotechnologies; 2020. https://clonoseq.com/technical-summary.
- Pulsipher M, et al. Blood. 2015;125(22):3501-8.
- Martinez-Lopez J, et al. Blood. 2014;123(20):3073-3079.
- Logan AC, et al. Biol Blood Marrow Transplant. 2014;20(9):1307-13.
- U.S. Food and Drug Administration. (2014). Blinatumomab [Press Release].
- Avet-Loiseau H. Am Soc Clin Oncol Educ Book. 2016; 35:e425-30.
- ClinicalTrials.gov. Search: clonoSEQ. Accessed May 5, 2020.