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Monitoring Treatment ResponseMonitoring Treatment Response

For patients receiving therapy for CML, the magnitude of reduction in tumor burden is a key prognostic indicator. Moreover, many patients treated with a Bcr-Abl inhibitor achieve a CCyR. For that reason, consistent and easily interpretable molecular monitoring results are needed to assess whether a patient with Ph+ CML has achieved or is making progress toward a desired response to therapy, and to ensure that a patient’s treatment is optimized over time.1-3

Achieving complete cytogenetic response (CCyR) alone does not guarantee survival4

The Ph+ chromosome can be detected by standard cytogenetic techniques in the vast majority of patients.5 However, cytogenetic testing has limits, particularly its ability to detect only up to a 2-log reduction in disease burden (or 1% BCR-ABL to control gene ratio on the international scale [IS]), which means residual disease may remain.6 This makes it impossible to quantify the full depth of response.6

Therefore, international guidelines recommend molecular monitoring with real-time quantitative polymerase chain reaction (RQ-PCR) testing every 3 months to assess BCR-ABL transcript levels. RQ-PCR can detect BCR-ABL transcript reductions of 5 to 6 logs in the blood.6,7


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Residual disease with CCyR at 12 months can increase the incidence of disease progression4

Studies have shown that more patients with CCyR at 12 months had disease progression than patients who achieved major molecular response (MMR) at 12 months.4


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Additional evidence reinforces the importance of achieving MMR early to improve long-term outcomes.8 In the IRIS study, it was shown that less residual disease at 12 months produces more durable event-free survival (EFS).9


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In addition, IRIS showed that 100% of patients who achieved an MMR by 12 months were free from progression to accelerated phase or blast crisis (AP/BC) for 8 years.11

With the ability to detect as little as 0.001% of remaining BCR-ABL transcripts, RQ-PCR testing can help better detect minimal residual disease to ensure treatment is optimized over time and improve long-term outcomes.6,11


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For current definitions, guidelines, and information about standardized molecular tests for Ph+ CML, click here.


Next: Advantages of Molecular Monitoring


Note: Before prescribing, please read full European Summary of Product Characteristics.

References

  1. Branford S, Rudzki Z, Harper A, et al. Imatinib produces significantly superior molecular responses compared to interferon alfa plus cytarabine in patients with newly diagnosed chronic myeloid leukemia in chronic phase. Leukemia. 2003;17(12):2401-2409.
  2. Paschka P, Muller MC, Merx K, et al. Molecular monitoring of response to imatinib (GLIVEC®)in CML patients pretreated with interferon alpha. Low levels of residual disease are associated with continuous remission. Leukemia. 2003;17(9):1687-1694
  3. Rosti G, Martinelli G, Bassi S, et al. Molecular response to imatinib in late chronic-phase chronic myeloid leukemia. Blood. 2004;1036:2284-2290.
  4. Iacobucci I, Saglio G, Rosti G, et al; for the GIMEMA Working Party on Chronic Myeloid Leukemia. Achieving a major molecular response at the time of a complete cytogenetic response (CCgR) predicts a better duration of CCgR in imatinib-treated chronic myeloid leukemia patients. Clin Cancer Res. 2006;12(10):3037-3042.
  5. Osarogiagbon UR, McGlave PB. Chronic myelogenous leukemia. Curr Opin Hematol. 1999;6(4):241-246.
  6. Radich JP. How I monitor residual disease in chronic myeloid leukemia. Blood. 2009;114(16):3376-3381.
  7. Baccarani M, Cortes J, Pane F, et al. Chronic myeloid leukemia: an update of concepts and management recommendations of European LeukemiaNet. J Clin Oncol. 2009;27(35):6041-6051.
  8. Palandri F, Iacobucci I, Soverini S, et al. Treatment of Philadelphia-positive chronic myeloid leukemia with imatinib: importance of a stable molecular response. Clin Cancer Res. 2009;15(3):1059-1063.
  9. Hughes TP, Hochhaus A, Branford S, et al. Reduction of BCR-ABL transcript levels at 6, 12, and 18 months (mo) correlates with long-term outcomes on imatinib (IM) at 72 mo: an analysis from the International Randomized Study of Interferon versus STI571 (IRIS) in patients (pts) with chronic phase chronic myeloid leukemia (CML-CP). Blood. 2008;112(11):Abstract 334.
  10. Data on file. Novartis Pharma AG. Basel, Switzerland.
  11. Deininger M, O’Brien SG, Guilhot F, et al. International randomized study of interferon and STI571 (IRIS) 8-year follow-up: Sustained survival and low risk for progression or events in patients with newly diagnosed chronic myeloid leukemia in chronic phase treated with imatinib. Poster presented at: 51st American Society of Hematology (ASH) Annual Meeting and Exposition; December 5-8, 2009; New Orleans, LA.