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MRD describes the very small number of cancer cells that remain in the body during or after treatment.1-4 Residual disease can be measured in many types of cancer. MRD is especially relevant in blood cancers, where new therapies can have improved responses. While patients can achieve remission, many will eventually experience relapse.5-9 Precisely measuring disease burden, even in the absence of symptoms, is fundamental to providing optimal care for patients.

Start a conversation about minimal residual disease (MRD)

Understanding and using MRD tests can give patients and doctors confidence that they are making clinical decisions based on data.

 

Learn more about MRD testing in blood cancer

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Studies have provided evidence for the clinical value of MRD testing in:

(ALL) Acute lymphoblastic leukemia10-12 (AML) Acute myeloid leukemia5,13 (CLL) Chronic lymphocytic leukemia14-17 (CML) Chronic myeloid leukemia9,18 (MM) Multiple myeloma19-21 (NHL) Non-Hodgkin’s lymphoma22-24

Is treatment achieving your patient’s goals?

In many types of blood cancers, undetectable MRD is associated with survival.16,18,19,25 MRD test results can predict patient outcomes because clinical relapse begins with molecular relapse.9,26,27 Decreasing MRD during treatment is a sign that treatment is effective.

Web resources

The survival of patients with pediatric acute lymphoblastic leukemia (ALL) has significantly improved in the last several decades. However, novel strategies to identify cases that are likely to respond poorly to treatment are still needed.

William G. Wierda, MD, PhD, D. B. Lane Cancer Research Distinguished Professor; section chief of Chronic Lymphocytic Leukemia; center medical director, Department of Leukemia, Division of Cancer Medicine; and executive medical director, The University of Texas

Thanks to the introduction of tyrosine kinase inhibitors (TKIs), chronic myeloid leukemia (CML) has been transformed from a deadly cancer into a treatable chronic illness. CML is identified by the fusion of two genes, which yields a gene product called BCR-ABL.

Clinicians should be measuring minimal residual disease (MRD) in their patients with acute myeloid leukemia (AML), because complete remission (CR) on its own is simply not enough, according to a presentation given at the 2018 Lymphoma & Myeloma congress.

It is not unusual for myeloma patients to live 10 years or more. Outcomes are influenced by patient factors, such as stage of the disease, chromosome changes, age, and other medical problems. Patients should discuss individual potential outcomes with their doctors.

The emergence of Bruton’s tyrosine kinase (BTK) inhibitors into the treatment landscape for mantle cell lymphoma (MCL) has improved patient outcomes over the past 6 years. Specifically, the use of BTK inhibitors results in higher overall response rates (ORRs), more

Should a treatment change be considered?

As new therapies become available, choosing the most effective treatment for each patient will become a new challenge. In the future, MRD testing will be used with a wider choice of treatments to confirm or change treatment based on individual patient responses.22,28

Selected publications

Current developments in molecular monitoring in chronic myeloid leukemia.

Minimal residual disease is an independent predictor for 10-year survival in CLL.

Role of minimal residual disease monitoring in acute promyelocytic leukemia treated with arsenic trioxide in frontline therapy.

Minimal residual disease in adult ALL: technical aspects and implications for correct clinical interpretation.

MRD testing in multiple myeloma: From a surrogate marker of clinical outcomes to an every-day clinical tool.

Role of minimal residual disease monitoring in acute promyelocytic leukemia treated with arsenic trioxide in frontline therapy.

What is the right balance between ongoing treatment and quality of life?

For some patients in remission, there may be a trade-off between the effectiveness of maintenance therapy and quality of life or preserving fertility. If the decision is made to discontinue maintenance therapy for a patient, MRD testing at multiple time points can be used to detect early signs of relapse.9,23,25,29

Organizations

An international society focused on advancing the understanding, diagnosis, treatment, and prevention of blood cancers.

The main agency of the U.S. government for cancer research and training.

A database of clinical studies conducted around the world provided by the U.S. National Library of Medicine.

An organization for myeloma patients to find, understand and join eligible clinical trials.

A patient-centric nonprofit organization for the chronic lymphocytic leukemia (CLL) community.

An organization for myeloma patients to find, understand and join eligible clinical trials.

A patient-driven nonprofit organization that empowers patients with myeloma at each step of their disease journey.

A clinical trials group supported by the National Cancer Institute and devoted exclusively to childhood and adolescent cancer research.

A society dedicated to blood cancer research, patient support, policy and advocacy.

A health organization seeking to improve care for patients with lymphoma through education, support services, and research investment.

A nonprofit organization focused on empowering, supporting, and improving health outcomes for young adults with cancer.

A charity dedicated to funding childhood cancer research.

A society dedicated to blood cancer research, patient support, policy and advocacy.

Do patients have enough knowledge to make plans?

MRD testing can provide data for shared decision making between doctors and patients. Along with other types of tests, consistently undetectable MRD results can give patients confidence to plan their lives.

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References

1. Glossary. In: Schwab M, Ed. Encyclopedia of Cancer. 3rd ed. Berlin, Germany: Springer-Verlag; 2011. https://link.springer.com/referencework/10.1007/978-3-642-16483-5. doi:10.1007/978-3-642-16483-5

2. National Cancer Institute. (n.d.). NCI Dictionary of Cancer Terms. Bethesda, MD: National Institutes of Health. https://www.cancer.gov/publications/dictionaries/cancer-terms/def/797387

3. Brüggemann M, Kotrova M. Minimal residual disease in adult ALL: technical aspects and implications for correct clinical interpretation. Blood Adv. 2017;1(25):2456-2466.

4. Thompson M, Brander D, Nabhan C, Mato A. Minimal residual disease in chronic lymphocytic leukemia in the era of novel agents: a review. JAMA Oncol. 2018;4(3):394-400.

5. Voso MT, Ottone T, Lavorgna S, et al., MRD in AML: The Role of New Techniques. Frontiers in Oncology. 2019;(9):655.

6. Terwilliger T, Abdul-Hay M. Acute lymphoblastic leukemia: a comprehensive review and 2017 update. Blood Cancer J. 2017;7(6):e577. doi:10.1038/bcj.2017.53.

7. Landgren O, Giralt S. MRD-driven treatment paradigm for newly diagnosed transplant eligible multiple myeloma patients. Bone Marrow Transplant. 2016;51(7):913-914.

8. Martinez-Lopez J, Blade J, Mateos MV, et al. Long-term prognostic significance of response in multiple myeloma after stem cell transplantation. Blood. 2011;118(3):529-534.

9. Radich JP. How I monitor residual disease in chronic myeloid leukemia. Blood. 2009;114(16):3376-3381.

10. Brüggemann M, Schrauder A, Raff T, et al; on behalf of the European Working Group for Adult Acute Lymphoblastic Leukemia (EWALL), International Berlin-Frankfurt-Münster Study Group (I-BFM-SG). Standardized MRD quantification in European ALL trials: proceedings of the Second International Symposium on MRD assessment in Kiel, Germany, 18-20 September 2008. Leukemia. 2010;24(3):521-535.

11. Ribera J-M, Oriol A, Morgades M, et al. Treatment of high-risk Philadelphia chromosome–negative acute lymphoblastic leukemia in adolescents and adults according to early cytologic response and minimal residual disease after consolidation assessed by flow cytometry: final results of the PETHEMA ALL-AR-03 trial. J Clin Oncol. 2014;32(15): 1595-1604, appendix.

12. Wood B, Wu D, Crossley B, et al. Measurable residual disease detection by high-throughput sequencing improves risk stratification for pediatric B-ALL. Blood. 2018;131(12):1350-1359.

13. De Angelis F, Breccia M. Molecular monitoring as a path to cure acute promyelocytic leukemia. Rare Cancers Ther. 2015;3:119-132.

14. Böttcher S, Ritgen M, Fischer K, et al. Minimal residual disease quantification is an independent predictor of progression-free and overall survival in chronic lymphocytic leukemia: a multivariate analysis from the randomized GCLLSG CLL8 trial. J Clin Oncol. 2012;30(9):980-988.

15. Santacruz R, Villamor N, Aymerich M, et al. The prognostic impact of minimal residual disease in patients with chronic lymphocytic leukemia requiring first-line therapy. Haematologica. 2014;99(5):873-880.

16. Kwok M, Rawstron AC, Varghese A, et al. Minimal residual disease is an independent predictor for 10-year survival in CLL. Blood. 2016;128(24):2770-2773.

17. Ringelstein-Harlev S, Fineman R. Minimal residual disease surveillance in chronic lymphocytic leukemia by fluorescence-activated cell sorting. Rambam Maimonides Med J. 2014;5(4):e0027. doi:10.5041/RMMJ.10161.

18. Soverini S, De Benedittis C, Mancini M, Martinelli G. Best practices in chronic myeloid leukemia monitoring and management. Oncologist. 2016;21(5):626-633.

19. Munshi NC, Avet-Loiseau H, Rawstron AC, et al., Association of minimal residual disease with superior survival outcomes in patients with multiple myeloma. JAMA Oncol. 2017;3(1):28-35. doi:10.1001/jamaoncol.2016.3160

20. Martinez-Lopez J, Lahuerta JJ, Pepin F, et al. Prognostic value of deep sequencing method for minimal residual disease detection in multiple myeloma. Blood. 2014;123(20):3073-3079.

21. Mateos M-V, Dimopoulos MA, Cavo M, et al; for the ALCYONE Trial Investigators. Daratumumab plus bortezomib, melphalan, and prednisone for untreated myeloma. N Engl J Med. 2018;378(6):518-528.

22. Herrera AF, Armand P. Minimal residual disease assessment in lymphoma: methods and applications. J Clin Oncol. 2017;35(34):3877-3887.

23. Kolstad A, Pedersen LB, Eskelund CW, et al; Nordic Lymphoma Group. Molecular monitoring after autologous stem cell transplantation and preemptive rituximab treatment of molecular relapse; results from the Nordic Mantle Cell Lymphoma studies (MCL2 and MCL3) with median follow-up of 8.5 years. Biol Blood Marrow Transplant. 2017;23(3): 428-435.

24. Armand P, Oki Y, Neuberg DS, et al. Detection of circulating tumour DNA in patients with aggressive B-cell nonHodgkin lymphoma. Br J Haematol. 2013;163(1):123-144.

25. Berry DA, Zhou S, Higley H, et al., Association of minimal residual disease with clinical outcome in pediatric and adult acute lymphoblastic leukemia. JAMA Oncol. 2017;3(7):e170580.

26. Chen X, Wood BL. How do we measure MRD in ALL and how should measurements affect decisions. Re: treatment and prognosis? Best Pract Res Clin Haematol. 2017;30(3):237-248.

27. Döhner H, Estey E, Grimwade D, et al., Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood. 2017;129(4):424-447.

28. Landgren O, Lu SX, Hultcrantz M. MRD testing in multiple myeloma: the main future driver for modern tailored treatment. Seminars in Hematology. 2018;55(1):44-50.

29. Kröger N, Miyamura K, Bishop MR. Minimal residual disease following allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2011;17(Suppl. 1):S94-S100.

30. Brüggemann M, Raff T, Kneba M. Has MRD monitoring superseded other prognostic factors in adult ALL? Blood. 2012;120(23):4470-4481.