Response-Related Predictors of Survival and of Treatment-Free Remission in CML

Abstract

Response to tyrosine kinase inhibitor (TKI) therapy in CML can be measured by haematological, cytogenetic and molecular criteria. Achieving haematological and cytogenetic response is still a desirable early measure of response. However measurement of the level of BCR-ABL1 transcripts in the blood by qRT-PCR, adjusted to the international scale (IS), is now the primary means of monitoring response. Achieving time-dependent molecular targets is a strong predictor of survival as well as indicating the longer-term prospects of achieving eligibility for treatment-free remission (TFR). Optimal response can be determined solely by the achievement and maintenance of time-dependent molecular response levels. Likewise, treatment failure is largely defined by a failure to achieve molecular milestones or loss of that molecular response, except in cases where treatment failure is evident by progression to advanced-phase disease. Treatment failure mandates a switch in therapy, usually to a more potent TKI, if possible. In between optimal response and treatment failure, there is a “warning category” where outcomes are generally inferior and therapeutic decisions are more complex. Recently, the importance of determining the dynamics of response, not just the BCR-ABL1 level at one specified time point, has been recognized, particularly when determining the probability of achieving sustained TFR in eligible patients.