Dynamics of Response to TKI Treatment

In patients who are responding to treatment with a tyrosine kinase inhibitor (TKI) the depth and time to response may be important factors. Improvement is initially manifested by the reduction/elimination of leukemic cells in peripheral blood (hematologic response), followed by the reduction/elimination of cells in the bone marrow containing the Philadelphia (Ph) chromosome (cytogenetic response). As patients achieve this increasing depth of response, there is a corresponding drop in the levels of bcr-abl transcripts in both peripheral blood and in the marrow (molecular response) (Figure).¹

Although initial treatment responses can be observed using hematologic evaluation, more sensitive methods for assessing CML disease status involving both cytogenetic assessment and molecular measurement of bcr-abl transcript levels are necessary to effectively monitor disease burden and treatment response over time.¹

In evaluating the dynamics of response to TKI treatment, investigators have concluded:

Measurement of bcr-abl transcripts is the most sensitive method of monitoring response; it can detect changes in disease burden that are not evident with cytogenetic testing

Several clinical studies have shown that early reductions in BCR-ABL transcript levels may predict the subsequent achievement of cytogenetic responses.^5,Early molecular response may also predict lack of disease progression. Long-term follow-up data in a large TKI clinical trial have shown that 100% of patients who achieved both CCyR and MMR at 12 months remained free from progression to accelerated phase (AP) or blast crisis (BC) at 5 years.²

Click to view and/or download the criteria for hematologic, cytogenetic, and molecular response.