Guidelines and Recommendations for Monitoring Ph+CML

Evidence obtained in clinical trials and post-approval setting with targeted therapy has prompted experts to formulate consensus recommendations for response assessment and treatment of patients with Ph+ CML.^1,2

European LeukemiaNet (ELN)

The (ELN), a panel of CML experts from 22 countries, has published recommendations proposing a schedule of response milestones for targeted therapy for Ph+ CML, including continued molecular monitoring during targeted therapy.

A rise in BCR-ABL transcript levels detected during targeted therapy for Ph+ CML is a warning sign and should trigger a subsequent, more stringent, RQ-PCR analysis.²

The ELN recommends the following testing schedule when monitoring treatment of CML patients³:

• Hematologic response
  • At diagnosis, then every 15 days until complete hematologic response (CHR) has been achieved and confirmed, then at least every 3 months or as required
• Cytogenetic response
  • At diagnosis, at 3 months, and at 6 months; then every 6 months until a CCyR has been achieved and confirmed, then every 12 months if regular molecular monitoring cannot be assured; always for occurrences of treatment failure and for occurrences of unexplained cytopenias*
• Molecular response by RQ-PCR
  • At diagnosis, every 3 months until MMR has been achieved and confirmed, then at least every 6 months
• Mutational analysis
  • In occurrences of suboptimal response or failure; recommended before changing to other tyrosine kinase inhibitors (TKIs) or other therapies

^*Fluorescence in situ hybridization (FISH) may be preferred over conventional cytogenetics as it can evaluate more cells and peripheral blood can be used instead of marrow. However, current data are based on conventional cytogenetics so FISH is only recommended prior to treatment to identify cases of Ph-, BCR-ABL+ CML, and those with variant translocations, Ph amplification, or del9q+.¹

ELN testing recommendations

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Using RQ-PCR testing effectively

Baseline (newly diagnosed Ph+ CML)

• BCR-ABL transcript levels should be measured at diagnosis to establish a baseline³
• Regular molecular monitoring over the course of disease can help facilitate treatment decisions⁴

Early response

• Diligent monitoring can help in the early identification of possible slow responders or adherence issues; monitoring also creates opportunity for discussion with patients and for evaluation⁴
• Measure transcript levels every 3 months if patients are responding to therapy³

CCyR achieved, but no MMR

• Routine cytogenetic testing may only detect residual disease up to a 1- to 2-log reduction in CML burden⁵
• Measure transcript levels every 3 to 6 months after CCyR to ensure a durable CCyR³

Rising levels of BCR-ABL transcripts³

• Evaluate for compliance
• If MMR has already been achieved, repeat PCR in 1 to 3 months
• If MMR has not been achieved, obtain bone marrow cytogenetics
• If transcript levels continue to rise, mutational testing should be considered
  • For resistant or less sensitive mutations, allogeneic stem cell transplantation is recommended

Learn more about the ELN

To download the ELN panel's recommendations for CML, click here. (Subscription to Blood required for free access to full text.)

Reviewing the Latest Recommendations in CML Management

The National Comprehensive Cancer Network (NCCN), a not-for-profit alliance of 20 leading cancer centers in the United States, publishes evidence-based clinical practice guidelines for CML. The guidelines detail specific recommendations based on patients’ cytogenetic responses to treatment. Also,the NCCN detail proposed indications for cytogenetics and PCR for BCR-ABL mRNA, and indications for Abl kinase domain mutation analysis.

To download the latest NCCN clinical practice guidelines for CML, click here to register.

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