Predictive value of in vitro mutation data to guide second-generation tyrosine kinase inhibitor selection: ready for prime time?

Overview

Significant advances in treatment and monitoring for patients with chronic myeloid leukemia have occurred over the last decade. With the introduction of the tyrosine kinase inhibitor imatinib, long-term outcomes have improved and new challenges, such as resistance, including mutations, have emerged. Research efforts into mutational analysis have intensified, with emphasis on the potential of using this technique to guide second-generation tyrosine kinase inhibitor selection. Although some data suggest that a small number of mutations may be associated with a less favorable response to treatment with one second-generation tyrosine kinase inhibitor versus another, these data need to be interpreted cautiously because they are derived primarily retrospectively from single-institution studies and a small number of patients. More research and clinical experience and a better understanding of the implications of in vitro data are needed before these data can be routinely incorporated into therapeutic decisions. Currently, there is no consensus on when to screen patients for mutations, what technique should be used, or how values should be reported. Selection of a second-generation tyrosine kinase inhibitor should therefore be based upon its toxicity profile in conjunction with the patient's comorbidities and the practitioner's experience.