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

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

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

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.