MRD can help you gain deeper insights into patients’ response to treatment1-3

Precisely measuring tumor burden and response to therapy are fundamental to providing confident care to patients with blood cancers4,5

The ability to track disease burden over time is an important component of personalized medicine.3,6,7

Active Treatment

  • Support treatment selection8
  • Assess treatment response9
  • Intensify/deintensify treatment8,10
  • Help inform need for additional treatment8

Remission

  • Confirm remission11
  • Monitor remission12
  • Inform frequency of monitoring5
  • Inform decision to stop maintenance5

Disease Recurrence

  • Detect recurrence13
  • Decide to reinitiate treatment8

MRD is a direct measure of disease3,14,15

Subclinical disease burden can remain in patients’ bodies after treatment, and patients can be MRD positive even if they are in clinical remission.16

Advances in the accuracy and sensitivity of MRD testing have helped improve clinicians’ ability to stratify risk in patients, predict and measure treatment response, monitor remission, and identify early recurrence.3,15,17,18

Light Microscopy19

From 1 cell in 20
to 1 cell in 100

when 1 million cells are tested

Flow Cytometry9

From 5 cells
in 1,000
to 1 cell
in 100,000

when 1 million cells are tested

ASO-PCR19

From 5 cells
in 100,000
to 1 cell
in 1,000,000

when 1 million cells are tested

Next Generation Sequencing (NGS)20

1 cell in
1,000,000

when 1 million cells are tested

It’s important to stress that an MRD negative result does not necessarily indicate the absence of disease in patients but means that the MRD test used did not detect cancerous cells within the tested sample. The amount of disease that is measurable depends on the testing method chosen, which underscores how essential it is to choose the right assessment tool, particularly when basing treatment decisions on its results.19,21

Sensitive and precise identification of MRD represents an evolution in disease burden assessment that can contribute to more personalized care.14,17,18,22

Defining MRD
References
  1. Logan AC, Zhang B, Narasimhan B, et al. Minimal residual disease quantification using consensus primers and high-throughput IGH sequencing predicts post-transplant relapse in chronic lymphocytic leukemia. Leukemia. 2013;27(8):1659-1665.
  2. Logan AC, Vashi N, Faham M, et al. Immunoglobulin and T-cell receptor gene high-throughput sequencing quantifies minimal residual disease in acute lymphoblastic leukemia and predicts post-transplant relapse and survival [published online for public access April 24, 2014]. Biol Blood Marrow Transplant. 2014;20(9):1307-1313. doi:10.1016/j.bbmt.2014.04.018
  3. 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.
  4. Vij R, Mazumder A, Klinger M, et al. Deep sequencing reveals myeloma cells in peripheral blood in majority of multiple myeloma patients. Clin Lymphoma Myeloma Leuk. 2014;14(2):131-139.
  5. Anderson KC, Auclair D, Kelloff GJ, et al. The role of minimal residual disease testing in myeloma treatment selection and drug development: current value and future applications [published online for public access April 20, 2017]. Clin Cancer Res. 2017;23(15):3980-3993. doi:10.1158/1078-0432.CCR-16-2895
  6. Schüler F, Dölken G. Detection and monitoring of minimal residual disease by quantitative real-time PCR. Clin Chim Acta. 2006;363(1-2):147-156.
  7. Herrera AF, Armand P. Minimal residual disease assessment in lymphoma: methods and applications. J Clin Oncol. 2017;35(34):3877-3887.
  8. Blincyto [package insert]. Thousand Oaks, CA: Amgen Inc; 2018.
  9. 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.
  10. Landgren O. MRD testing in multiple myeloma: from a surrogate marker of clinical outcomes to an every-day clinical tool. Semin Hematol. 2018;55(1):44-50.
  11. Dimopoulos MA, Oriol A, Nahi H, San-Miguel J, et al. Daratumumab, lenalidomide, and dexamethasone for multiple myeloma. N Engl J Med. 2016;375:1319-1331.
  12. 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.
  13. Pulsipher MA, Carlson C, Langholz B, et al. IgH-V(D)J NGS-MRD measurement pre- and early post-allotransplant defines very low- and very high-risk ALL patients. Blood. 2015;125(22):3501-3508.
  14. Berry DA, Zhou S, Higley H, et al. Association of minimal residual disease with clinical outcome in pediatric and adult acute lymphoblastic leukemia: a meta-analysis [published online July 13, 2017]. JAMA Oncol. 2017;3(7):e170580. doi:10.1001/jamaoncol.2017.0580
  15. Sherrod AM, Hari P, Mosse CA, Walker RC, Cornell RF. Minimal residual disease testing after stem cell transplantation for multiple myeloma. Bone Marrow Transplant. 2016;51(1):2-12.
  16. Thompson PA, Tam CS, O’Brien SM, et al. Fludarabine, cyclophosphamide, and rituximab treatment achieves long-term disease-free survival in IGHV-mutated chronic lymphocytic leukemia. Blood. 2016;127(3):303-309.
  17. Flores-Montero J, Sanoja-Flores L, Paiva B, et al. Next Generation Flow for highly sensitive and standardized detection of minimal residual disease in multiple myeloma. Leukemia. 2017;31(10):2094-2103.
  18. Brüggemann M, Raff T, Kneba M. Has MRD monitoring superseded other prognostic factors in adult ALL? Blood. 2012;120(23):4470-4481.
  19. van Dongen JJM, van der Velden VHJ, Brüggemann M, Orfao A. Minimal residual disease diagnostics in acute lymphoblastic leukemia: need for sensitive, fast, and standardized technologies. Blood. 2015;125(26):3996-4009.
  20. Carlson CS, Emerson RO, Sherwood AM, et al. Using synthetic templates to design an unbiased multiplex PCR assay. Nat Commun. 2013;4:2680.
  21. 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.
  22. Mailankody S, Korde N, Lesokhin AM, et al. Minimal residual disease in multiple myeloma: bringing the bench to the bedside. Nat Rev Clin Oncol. 2015;12(5):286-295.