Complementary Value of Minimal Residual Disease Assessments by NGS and MFC for the Study of Hematologic Malignancies
December 1, 2020 | 11 am to 12 pm EDT
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Measurable residual disease, also called minimal residual disease (MRD) refers to persistent leukemic cells in the blood or bone marrow of cancer patients during or after treatment. MRD tests are routinely used to study and track hematologic malignancies. MRD is also emerging as a trial outcome measure in various hematologic disorders including chronic lymphocytic leukemia (CLL), multiple myeloma and acute myeloid leukemia (AML).1,2 Hence, sensitive MRD tests are needed to guide optimal cancer treatments, measure response to treatment, and for surveillance. MRD testing guidelines and techniques vary based on the type of hematologic cancer and targeted therapies available for testing. Several methods of MRD assessment are available in clinical and research settings. Traditionally, MRD assessment was performed using morphologic and imaging techniques which have limited sensitivities compared to multiparameter flow cytometry (MFC), quantitative polymerase chain reaction (qPCR) and next generation sequencing (NGS). While each technique has advantages and limitations, certain MRD methodologies are better suited for specific disease states and will likely benefit from a combinations of tests.
MFC detection of Leukemia-associated immunophenotypes (LAIPs) is often used for diagnosis and can be useful for tracking subsequent samples. In addition, normal cell populations in bone marrow, demonstrate consistent patterns of antigen expression, so determination of aberrancy is based on a comparison to normal which can be helpful to detect immunophenotypic shift due to clonal evolution during treatment, or when prior immunphenotypic information is not available. Although the sensitivity of flow-based MRD testing is lower than molecular tests, there are several advantages of MFC which will be discussed.
Molecular based MRD methods are highly sensitive techniques with NGS sensitivity reaching up to 1x10-6 with sufficient DNA input. NGS is increasingly being used as an important tool for the molecular characterization of hematologic diseases at the time of initial diagnosis, to identify prognostic and predictive or therapeutically targetable genetic changes, and to assess MRD. A targeted NGS MRD method enables simultaneous profiling of several gene rearrangements of interest. While NGS has many benefits and is potentially applicable to all hematologic malignancies, there are challenges and limitations. In this webinar we will explore the advantages and disadvantages of MFC and NGS-based MRD.
1 Clare FJ et al. The Application of Minimal Residual Disease in Hemato-Oncology: A Review of Its Current Utility in Trials, Regulatory Decisions and Clinical Practice. Blood 2017; 130 (Supplement 1): 5630.
2 Luskin MR, et al. Targeting minimal residual disease: a path to cure? Nat Rev Cancer. 2018 Apr;18(4):255-263.
- Explore various methods, tools and criteria used to evaluate MRD in hematologic malignances
- Understand the technical advantages and disadvantages of multiparameter flow cytometry and NGS based MRD testing
- Learn how NGS-MRD testing can complement MFC testing
Ola Landgren, M.D., PhD
Professor of Medicine, Chief Attending Physician, Myeloma Service
Memorial Sloan Kettering Cancer Center
Dr. Ola Landgren is Professor of Medicine and Chief Attending Physician of the Myeloma Service at Memorial Sloan Kettering Cancer Center (MSKCC) in New York City. He is one of the world leaders in the field of early treatment strategies and molecular- and cell-based monitoring of minimal residual disease (MRD) detection in multiple myeloma and its precursor states. Dr. Landgren leads a translational research program at MSKCC designed to discover new treatment paradigms integrating modern therapy and novel MRD assays. He has designed and led the definitive study showing that all multiple myeloma patients are preceded by a precursor stage. As part of his ongoing research program, Dr. Landgren is studying molecular mechanisms underlying the trajectory from precursor to full-blown multiple myeloma with the goal to develop treatment strategies aiming to delay, prevent, and ultimately define a cure for multiple myeloma.
Dr. Landgren has published over 250 peer-reviewed publications and he is a frequently invited speaker at national and international hematology conferences. He serves on several research committees and editorial boards for scientific journals.
Swati Shah M.D.
Lead Hematopathologist, Flow Cytometry Laboratory
Dr. Swati Shah is a Lead Hematopathologist at LabPMM (Laboratory for Personalized Molecular Medicine) in San Diego, California. She oversees the flow cytometry laboratory where she is leveraging flow cytometry based MRD assays to ameloriate personalized patient care.
Dr. Shah is a board certified, practicing pathologist with 20 years of broad experience in anatomic, clinical pathology and hematopathology. She has worked at academic and community hospitals, as well as at high-volume outpatient reference diagnostic laboratory settings in the United States. Her core specialty and passion is hematopathology, with more than 15 years of comprehensive diagnostic hematopathology experience in leukemia and lymphoma diagnoses, as well as MRD testing utilizing traditional morphologic evaluation of tissues along with ancillary techniques such as flow cytometric immunophenotyping, immunohistochemistry, cytogenetic and molecular technologies. Her experience in pathology also includes prognostic and predictive testing in solid tumor oncology, image analysis, research and assay development. Dr. Shah has held various positions as Director of Hematopathology, Assistant Head of Clinical Pathology, Senior and Lead Hematopathologist. She is a Fellow of the College of American Pathologists and has coauthored a number of peer reviewed scientific publications.
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