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ONGOING MANAGEMENT AND MONITORING

Monitoring treatment response

For patients receiving long-term therapy for Ph+ CML, ongoing monitoring is 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

RQ-PCR quantifies BCR-ABL transcripts in peripheral blood and can detect low levels of residual disease that can remain after 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 as a routine standard of care for patients with Ph+ CML, as a way to measure minimal levels of residual disease.¹

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To learn more about RQ-PCR monitoring, visit the CML Alliance.

Importance of adherence

Clinical experience with imatinib has shown us that adherence to oral Ph+ CML therapy is critical to achieving and maintaining the best response.^4,5

Two recent clinical trials, the Hammersmith study and the ADAGIO study, demonstrate that adherence to Ph+ CML therapy is critical to achieving and maintaining optimal response.^4,5 In fact, evidence demonstrates that missing more than 2 or 3 daily doses of imatinib each month can negatively impact response.^4,5

The Hammersmith study: summary results⁴

Study design

• 87 English patients completed the study
• Patients were in CCyR, had Ph+ CML-CP, and had received oral therapy for at least 2 years
• Adherence was monitored over 90 days

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Key findings

• Adherence rate (>90% or ≤90%) was strongly associated with the 6-year probability of MMR, 4-log reduction in BCR-ABL, complete molecular response (CMR), and response at 18 months
• Probability of MMR for the 23 patients with an adherence rate ≤90% was 13.9%; for the 64 patients with an adherence rate >90%, it was 93.7% (P<0.001)
• 90% adherence is equivalent to missing approximately 2 to 3 tablets per month

Additional findings

• Adherence was poor after imatinib dose increase beyond 400 mg per day
• Young patients were more likely to have a lower adherence rate
• Unexplained 5-fold increases in BCR-ABL transcript levels were predictive of poor adherence
• Low adherence was also associated with side effects; health care providers should regularly ask patients if they are experiencing such effects

Conclusions

• Adherence is critical for achieving molecular responses; adherence rate was the only independent factor that predicted CMR
• Side effects can impact adherence
• No CMR was observed when adherence was ≤90%; no MMR was observed when adherence was ≤80%

The ADAGIO study: summary results⁵

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Study design

• 169 Belgian patients completed the study
• Patients had Ph+ CML-CP for an average of 4 years and were receiving oral therapy
• Adherence (taking medicine every day as directed by the physician) was evaluated over 90 days

Results

• Adherence greatly influenced response

Additional findings

• Failure to adhere was related to the patient, physician-patient relationship, and treatment center
• Patients who function well and those who have taken oral CML therapy for a long time may become more lax about taking their medication

Conclusions

• More patients failed to adhere to therapy than they, their physicians, and their family members realized
• Poor adherence was related to lower response rates
• Health care providers can affect how patients adhere to therapy

References:
1. Baccarani M, Pane F, Saglio G. Monitoring treatment of chronic myeloid leukemia. Haematologica. 2008;93(2):161-169.
2. Radich JP. How I monitor residual disease in chronic myeloid leukemia. Blood. 2009;114(16):3376-3381.
3. Hughes T, Deininger M, Hochhaus A, et al. Monitoring CML patients responding to treatment with tyrosine kinase inhibitors: review and recommendations for harmonizing current methodology for detecting Bcr-Abl transcripts and kinase domain mutations and for expressing results. Blood. 2006;108(1):28-37.
4. Marin D, Bazeos A, Mahon F-X, et al. Adherence is the critical factor for achieving molecular responses in patients with chronic myeloid leukemia who achieve complete cytogenetic responses on imatinib. J Clin Oncol. 2010;28(14):2381-2388.
5. Noens L, van Lierde M-A, De Bock R, et al. Prevalence, determinants, and outcomes of nonadherence to imatinib therapy in patients with chronic myeloid leukemia: the ADAGIO study. Blood. 2009;113(22):5401-5411.
6. TASIGNA^® (nilotinib) Summary of Product Characteristics. Basel, Switzerland: Novartis Pharma AG; June 2011.