Testing for Measurable/Minimal Residual Disease (MRD)

Author: Christina Bach, MBE, LCSW, OSW-C
Last Reviewed: November 16, 2022

Measurable or minimal residual disease (MRD) testing is used to see if the cancer treatment is working and to guide further treatment plans. MRD testing is mainly used in blood cancers (leukemia, lymphoma and myeloma), but is being studied in other cancers. It is a type of personalized medicine, because the results can be used to tailor your treatment plan.

What can the MRD test find?

This test can find even the smallest amount of cancer cells that may be left in the body after treatment. This can:

  • Show how well your cancer has responded to the treatment you received.
  • Do a better job of finding out if you are in remission than other tests.
  • Find a cancer recurrence (when the cancer comes back) sooner than other tests.

MRD tests use highly sensitive methods, including multi-parametric flow cytometry and polymerase chain reaction (PCR). These methods look for any remaining cancer cells that cannot be seen in routine tests. This test can find even 1 cancer cell among 1 million normal cells.

MRD testing is also useful in clinical trials for new medicines. MRD can show how well the medicine is working at treating the cancer without having to wait months to see if the cancer returns.

Does insurance cover this test?

Because this test is highly specialized, not all labs can perform MRD testing. This may result in the test needing to be sent to an out of network provider for testing. This can result in out of network fees from your insurance. Be sure to ask about insurance coverage and costs before the test is done. The testing may also require prior authorization.

MRD Testing in Specific Cancers

MRD and Acute Lymphocytic Leukemia (ALL)

  • Part of routine testing in the treatment of pediatric and most adult ALL.
  • Can detect relapse earlier than other tests. This allows for earlier treatment if relapse is suspected.
  • Studies show that MRD is the best way to predict what treatments will be most helpful after the induction phase ALL treatment.
  • MRD can also help identify patients most at risk for ALL relapse. These patients may have the best chance for a cure with a bone marrow transplant. Patients with good MRD response may be able to avoid transplant.

Chronic Lymphocytic Leukemia (CLL)

  • PCR and flow cytometry are used for testing.
  • MRD negative patients may have better outcomes.
  • MRD positive patients may benefit from more intense treatment, consolidation, and maintenance strategies.

Chronic Myeloid Leukemia (CML)

  • Testing is done using PCR.
  • PCR can detect if the Philadelphia chromosome is present.
  • Results can help decide which treatment is best, including if tyrosine kinase inhibitor therapy should be changed or stopped.

MRD and Lymphoma

  • Used in follicular, mantle cell, and large B-cell lymphoma.
  • Helps find the patients who are at higher risk of their cancer not responding to treatment or of relapsing. These patients can then receive more intensive treatment and earlier intervention.

MRD and Multiple Myeloma

  • MRD testing in myeloma uses three tools: flow cytometry, NextGen sequencing (genetic markers) and imaging to determine a positive or negative MRD. These tests are performed over time. The best tool has not yet been determined and there is no standard of care yet developed.
  • Researchers are working on when MRD testing should be used in people with myeloma.
  • Research is focusing on how to use MRD testing at diagnosis to guide treatment planning and if therapy can be stopped if MRD is negative.

References

Chase, M.L. & Armand, P. (2017). Minimal residual disease in non-Hodgkin lymphoma-current applications and future directions. British Journal of Haematology, 180, 177-180.

Hoelzer, D. (2017). Clinical Applications and Pitfalls of MRD in ALL. Clinical Lymphoma, Myeloma and Leukemia, 17, S9-S11.

Juul-Dam, K. L., Nyvold, C. G., Ommen, H. B., Jonsson, O. G., Lausen, B., Jahnukainen, K., & Hasle, H. (2015). qPCR MRD Monitoring in Peripheral Blood May Predict Hematological Relapse in Pediatric Acute Myeloid Leukemia. Blood, 126, 3749

Leukemia and Lymphoma Society. Minimal Residual Disease. Found at https://www.lls.org/sites/default/files/National/USA/Pdf/Publications/FS35_MRD_Final_2019.pdf

van der Velden, V. H., Noordijk, R., Brussee, M., Hoogeveen, P. G., Homburg, C., de Haas, V., ... & van Dongen, J. J. (2014). Minimal residual disease diagnostics in acute lymphoblastic leukaemia: impact of primer characteristics and size of junctional regions. British journal of haematology, 164(3), 451-453.

van Dongen, J. J., van der Velden, V. H., Brüggemann, M., & Orfao, A. (2015). Minimal residual disease (MRD) diagnostics in acute lymphoblastic leukemia (ALL): need for sensitive, fast and standardized technologies. Blood,125(26), 3996-4009.

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