Chronic myeloid leukemia (CML) is a type of blood cancer diagnosed by the presence of the “Philadelphia chromosome,” an abnormal translocation between chromosomes 9 and 22. This creates a gene fusion (BCR-ABL) that results in uncontrolled myeloid cell growth. However, thanks to a class of drugs known as tyrosine kinase inhibitors, CML has become easier to manage through routine monitoring of BCR-ABL.

Monitoring gene fusions

 

BCR-ABL monitoring informs physicians of a patient’s disease stage. Patients that respond well to drugs may have their disease classified as a minimal detectable disease (MDD) or minimal residual disease (MRD). Stable BCR-ABL levels at MRD is an indicator of a stable disease. A change to BCR-ABL levels indicates disease progression.

Current methods for monitoring BCR-ABL have limited sensitivity and significant variability, especially at low BCR-ABL levels, which may delay detection of disease progression and impact changes to disease management. This limited sensitivity also interferes with when physicians can safely discontinue a patient’s therapy. 50 percent of patients monitored under these current methods and whose therapy is stopped will experience relapse and disease progression. Thus, a better method for BCR-ABL monitoring is needed.

Available testing

Digital PCR technology improves the sensitivity and reproducibility of BCR-ABL detection and quantification. Digital PCR separates a sample into thousands of discrete partitions and analyzes each one independently, enabling lower levels of BCR-ABL to be quantified. This may inform physicians about their patient’s disease status, potentially improving patient outcomes.

PCR-based BCR-ABL tests are available in the market today, and a digital PCR-based test will soon arrive in clinics across the United States. The digital PCR test currently under FDA review is not indicated, nor has the criteria been established to determine when therapy can be stopped. However, the low-level detection of BCR-ABL may help physicians to provide their patients with the best possible treatment.