Understanding Clinical Endpoints In Measurable Residual Disease

Welcome to measurable residual disease (MRD) focus. Explore the cutting-edge updates in MRD by disease type, including expert interviews from major international congresses, podcasts and e-learning.

MRD is the term used to describe a small number of cancer cells remaining in patients following treatment, which are below the level of routine morphological detection1,2. Even when a patient is in remission it is possible for them to be ‘MRD positive’. The level of MRD can, theoretically, be used as a prognostic indicator to determine treatment efficacy and to detect cancer recurrence. MRD status is now increasingly measured as an endpoint in clinical trials for haematological malignancies, with the goal of treatment being MRD negativity. Indeed, the evidence suggests that in many haematological cancers, achieving MRD negativity in patients results in better clinical outcomes and is often an important psychological milestone for patients3-6.

The determination of MRD is made by detecting tumor-specific DNA, RNA or proteins, and is primarily performed using next-generation sequencing or multidimensional flow cytometry7-10. Owing to developments in MRD testing tools and technologies, MRD testing is increasingly being integrated into clinical practice outside of trials7,11,12. Therefore, although there are still questions remaining, it is important that clinicians understand when and how to use MRD testing for the optimal management of their patients.

  1. Ossenkoppele G, Schuurhuis GJ. MRD in AML: time for redefinition of CR? Blood. 2013 Mar 21; 121(12): 2166-2168.
  2. Ravandi F, Walter RB, Freeman SD. Evaluating measurable residual disease in acute myeloid leukemia. Blood Adv. 2018 Jun 12; 2(11): 1356-1366.
  3. Kwok M, Rawstron AC, Varghese A, et al. Minimal residual disease is an independent predictor for 10-year survival in CLL. Blood. 2016 Dec 15; 128(24): 2770-2773.
  4. Galimberti S, Luminari S, Ciabatti E, et al. Minimal residual disease after conventional treatment significantly impacts on progression-free survival of patients with follicular lymphoma: the FIL FOLL05 trial. Clin Cancer Res. 2014 Dec 15; 20(24): 6398-405.
  5. Freeman SD, Virgo P, Couzens S, et al. Prognostic relevance of treatment response measured by flow cytometric residual disease detection in older patients with acute myeloid leukemia. J Clin Oncol. 2013 Nov 10; 31(32): 4123-31.
  6. Rawstron AC, Child JA, de Tute RM, et al. Minimal residual disease assessed by multiparameter flow cytometry in multiple myeloma: Impact on outcome in the Medical Research Council Myeloma IX Study. J Clin Oncol. 2013 Dec 1; 31: 2540-2547.
  7. van Dongen JJ, van der Velden VH, Brüggemann M, et al. Minimal residual disease diagnostics in acute lymphoblastic leukemia: need for sensitive, fast, and standardized technologies. Blood. 2015 Jun 25; 125(26): 3996-4009.
  8. Cloos J, Harris JR, Janssen JJWM, et al. Comprehensive Protocol to Sample and Process Bone Marrow for Measuring Measurable Residual Disease and Leukemic Stem Cells in Acute Myeloid Leukemia. J Vis Exp. 2018 Mar 5; (133).
  9. Schweighofer CD, Hallek M, Wendtner CM. Eradication of minimal residual disease in chronic lymphocytic leukemia. Curr Hematol Malig Rep. 2008 Jan; 3(1): 54-60.
  10. Nyvold CG. Critical methodological factors in diagnosing minimal residual disease in hematological malignancies using quantitative PCR. Expert Rev Mol Diagn. 2015 May; 15(5): 581-4.
  11. Grimwade D, Freeman SD. Defining minimal residual disease in acute myeloid leukemia: which platforms are ready for “prime time”? Blood. 2014 Dec 5; 124(23): 3345-3355.
  12. Tomuleasa C, Selicean C, Cismas S, et al. Minimal residual disease in chronic lymphocytic leukemia: A consensus paper that presents the clinical impact of the presently available laboratory approaches. Crit Rev Clin Lab Sci. 2018 Aug; 55(5): 329-345.
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