Molecular monitoring in chronic myeloid leukemia - How low can you go?

Abstract

Molecular monitoring of BCR-ABL1 transcripts for patients with chronic myeloid leukemia (CML) is now used to assess response to tyrosine kinase inhibitors (TKIs), including treatment failure that mandates a change of therapy. Therefore, many centers have adopted the molecular technique for measuring BCR-ABL1 and rely on conversion of values to the international reporting scale for appropriate clinical interpretation. However, the technique has a degree of inherent variability despite standardized procedures, which means care should be taken by the clinician when assessing response based on BCR-ABL1 cutoff limits. The last few years have witnessed the emergence of a new molecular response target, which is the achievement and maintenance of a deep molecular response. The ability to achieve treatment-free remission for some patients has shifted the relevant boundary for molecular response. However, the definitive safe BCR-ABL1 transcript level and length of the maintenance phase after which treatment cessation can be attempted has not yet been determined. For patients with TKI resistance, BCR-ABL1 kinase domain mutation analysis remains an essential assessment to guide therapy. Furthermore, low-level mutation detection is clinically relevant for response prediction to subsequent TKI therapy for some patients. Multiple low-level mutations may be a biomarker of a clonally diverse disease with the propensity for resistance evolution. Overall, molecular monitoring, including low-level monitoring is a fundamental component of management for patients with CML.