DESCRIPTION
Measurable residual disease or minimal residual disease (MRD) refers to residual clonal cells that are still in the blood or bone marrow after treatment for hematologic malignancies. It is typically assessed using flow cytometry (FC) or polymerase chain reaction that can detect 1 clonal cell in 100,000 cells. Next-generation sequencing (NGS) is being proposed to improve the health outcomes in individuals who have been treated for hematological malignancies (e.g., acute lymphoblastic leukemia (ALL), chronic lymphoblastic leukemia (CLL), multiple myeloma (MM), diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL)) as it can detect 1 leukemic cell out of 1,000,000 cells.
The clonoSEQ® minimal residual disease test is offered by Adaptive Biotechnologies, previously marketed as clonoSIGHT™ (Sequenta) in 2015. In 2018, clonoSEQ®, received de novo clearance from the Food and drug administration (FDA) for individuals with ALL. In 2020 it received marketing clearance for CLL.
POLICY
Next-generation sequencing to detect measurable residual disease is considered medically necessary if the medical appropriateness criteria are met. (See Medical Appropriateness below.)
Next-generation sequencing to detect measurable residual disease, including, but not limited to, the following is considered investigational:
Diffuse large B-cell lymphoma
MEDICAL APPROPRIATENESS
Next-generation sequencing (e.g., clonoSEQ) to detect measurable residual disease is considered medically appropriate if ANY ONE of the following are met:
IMPORTANT REMINDERS
Any specific products referenced in this policy are just examples and are intended for illustrative purposes only. It is not intended to be a recommendation of one product over another and is not intended to represent a complete listing of all products available. These examples are contained in the parenthetical e.g. statement.
We develop Medical Policies to provide guidance to Members and Providers. This Medical Policy relates only to the services or supplies described in it. The existence of a Medical Policy is not an authorization, certification, explanation of benefits or a contract for the service (or supply) that is referenced in the Medical Policy. For a determination of the benefits that a Member is entitled to receive under his or her health plan, the Member's health plan must be reviewed. If there is a conflict between the Medical Policy and a health plan or government program (e.g., TennCare), the express terms of the health plan or government program will govern.
ADDITIONAL INFORMATION
The evidence available on NGS for detection of MRD in diffuse large B-Cell lymphoma and mantle cell lymphoma are lacking clinical validity or utility.
SOURCES
American Cancer Society. (2024, February). Types of B-cell lymphoma. Retrieved November 11, 2024 from www.cancer.org.
BlueCross BlueShield Association. Evidence Positioning System. (1:2024). Next-generation sequencing for the assessment of measurable residual disease. (2.04.147). Retrieved November 5, 2024 from www.bcbsaoca.com/eps/. (29 articles and/or guidelines reviewed)
Cavo, M., San-Miguel, J., Usmani, S.Z., Weisel, K., Dimopoulos, M.A., Avet-Loiseau, H., et al. (2022). Prognostic value of minimal residual disease negativity in myeloma: combined analysis of pollux, castor, alcyone, and maia. Blood, 139 (6), 835- 844. (Level 2 evidence)
CMS.gov: Centers for Medicare & Medicaid Services. Palmetto GBA. (2020, January). Next Generation Sequencing (NGS). (NCD 90.2). Retrieved November 11, 2024 from htttps://www.cms.gov.
Costa, L.J., Chhabra, S., Medvedova, E., Dholaria, B.R., Schmidt, T.M., Godby, K.N., et al. (2023). Minimal residual disease response-adapted therapy in newly diagnosed multiple myeloma: final report of the multicenter, single arm, phase 2 master trial. The Lancet Haematology, 10 (11), e890-e901. (Level 2 evidence)
Martinez-Lopez, J., Wong, S.W., Shah, N., Bahri, N., Zhou, K., Sheng, Y., et al. (2020). Clinical value of measurable residual disease testing for assessing depth, duration, and direction of response in multiple myeloma. Blood Advances, 4 (14), 3295-3301. (Level 5 evidence)
Munir, T., Moreno, C., Owen, C., Follows, G., Benjamini., O., Janssens, A., et al. (2023). Impact of minimal residual disease on progression free survival outcomes after fixed-duration ibrutinib-venetoclax versus chlorambucil-obinutuzumab in the glow study. Journal of Clinical Oncology, 41 (21), 3689-3699. (Level 3 evidence)
National Cancer Institute. (2024, March). Acute Lymphoblastic Leukemia Treatment (PDQ®)- Health Professional Version. Retrieved November 11, 2024 from https://www.cancer.gov/.
National Cancer Institute. (2024, March). Chronic Lymphocytic Leukemia Treatment (PDQ®)- Health Professional Version. Retrieved November 11, 2024 from https://www.cancer.gov/.
National Comprehensive Care Network. (2024. August). NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®). B-cell lymphomas. Retrieved November 7, 2024 from the National Comprehensive Cancer Network.
National Comprehensive Care Network. (2024. July). NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®). Acute lymphoblastic leukemia. Retrieved November 7, 2024 from the National Comprehensive Cancer Network.
National Comprehensive Care Network. (2024. October). NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®). Chronic lymphocytic leukemia/small lymphocytic lymphoma. Retrieved November 7, 2024 from the National Comprehensive Cancer Network.
National Comprehensive Care Network. (2024. September). NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®). Multiple Myeloma. Retrieved November 7, 2024 from the National Comprehensive Cancer Network.
Stefania, O., Genuardi, E., Paris, L., D’Agostino, M., Rogers, J., Rota-Scalabrini, D., et al. (2023). Prospective evaluation of minimal residual disease in the phase II forte trial: a head-to-head comparison between multiparameter flow cytometry and next generation sequencing. EClinical Medicine, 60, 102016. (Level 2 evidence)
U.S. Food and Drug Administration. (2020, August). Center for Devices and Radiological Health. De novo Notification Database. DEN170080. Retrieved November 8, 2024 from https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/denovo.cfm?ID=DEN17008.
U.S. Food and Drug Administration. (2020, August). Center for Devices and Radiological Health. 510(k) Premarket Notification Database. K200009. Retrieved November 8, 2024 from http://www.fda.gov/scripts/cdrh/dfdocs/dfpmn/pmn.cfm?id=K200009.
ORIGINAL EFFECTIVE DATE: 3/4/2025
MOST RECENT REVIEW DATE: 3/4/2025
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Policies included in the Medical Policy Manual are not intended to certify coverage availability. They are medical determinations about a particular technology, service, drug, etc. While a policy or technology may be medically necessary, it could be excluded in a member's benefit plan. Please check with the appropriate claims department to determine if the service in question is a covered service under a particular benefit plan. Use of the Medical Policy Manual is not intended to replace independent medical judgment for treatment of individuals. The content on this Web site is not intended to be a substitute for professional medical advice in any way. Always seek the advice of your physician or other qualified health care provider if you have questions regarding a medical condition or treatment.
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