Monitoring CML treatment response1-3

For patients receiving long-term therapy for Philadephia chromosome-positive chronic myeloid leukemia (Ph+ CML), ongoing monitoring is needed to assess whether they have achieved or are making progress toward a desired response to therapy and to ensure that their treatment is optimized over time.1-3

Real-time quantitative polymerase chain reaction (RQ-PCR) quantifies BCR-ABL transcripts in peripheral blood and can detect low levels of residual disease that remain after a complete cytogenetic response (CCyR) has been achieved.1-3 Rising levels of BCR-ABL transcripts may be an early indicator of poor adherence or emerging resistance.2,3

ELN recommendations support molecular monitoring every 3 months until a major molecular response (MMR) has been achieved, and then every 3 to 6 months thereafter, as a way to measure low levels of residual disease.4

Achievement of molecular milestones is associated with long-term outcomes

Early molecular response (EMR) at 3 months is associated with significantly higher rates of overall survival (OS) at 8 years5:

  • Achievement of MMR is associated with higher rates of EFS6 and PFS7
  • Achieving a molecular response with a 4.5-log reduction in BCR-ABL transcripts from baseline (MR4.5) at 4 years was associated with significantly higher OS than CCyR8

Molecular milestones can be detected only with IS RQ-PCR

Cytogenetic testing lacks the sensitivity to detect achievement of MMR or MR4.52:

  • Testing on the International Scale (IS) enables different laboratories to consistently compare BCR-ABL levels to a standardized baseline9
  • IS RQ-PCR can detect and quantify BCR-ABL transcripts from 1 CML cell in as many as 1,000,000 normal cells2

European LeukemiaNet recommendations for response to first-line tyrosine kinase inhibitor therapy1*

European Leukemia Net TKI Therapy Guidelines

*Molecular response is best assessed according to the International Scale (IS). It is expressed and reported as BCR-ABL% on a log scale, where 10%, 1%, 0.1%, and 0.0032% correspond to a decrease of 1, 2, 3, and 4.5 logs, respectively, below the standard baseline that was used in the IRIS study.1

  1. Baccarani M, et al. Haematologica. 2008;93(2):161-169.
  2. Radich JP. Blood. 2009;114(16):3376-3381.
  3. Hughes T, et al. Blood. 2006;108(1):28-37.
  4. Baccarani M, et al. Blood. 2013;122(6):872-884.
  5. Marin D, et al. J Clin Oncol. 2012;30(3):232-238.
  6. Press RD, et al. Clin Cancer Res. 2007;13:6136-6143.
  7. Hughes TP, et al. New Engl J Med. 2003;349:1423-1432.
  8. Hehlmann R, et al. J Clin Oncol. 2014;32(5):415-423.
  9. Müller MC, et al. Leukemia. 2009;23(11):1957-1963.