How I evaluate and treat resistance and relapse in CML

As evidenced by the excellent survival outcomes, chronic myeloid leukemia treatment in the era of tyrosine kinase inhibitors (TKIs) is often successful. However, when response milestones are not met or lost, treatment decision-making may be challenging. The availability for first-, second-, or subsequent-line use of 6 different TKIs, each with definite and often nonoverlapping features in terms of mechanism of action, potency, activity against resistance mutations, and tolerability profile provides a reassuring opportunity to rescue an optimal response, but it must be exploited carefully to avoid hasty or inappropriate choices. When and how to sequence TKIs, and whether and when to consider transplant are very important issues. “One-for-all” rules cannot be formulated, because for each individual patient the decision process requires investigation and integration of a series of clinical and biological factors. After discussing how resistance is defined, we aim here to provide practical guidance to therapeutic reassessment, discussing which laboratory investigations should be performed, how they should be interpreted, which additional clinical considerations are mandatory, and how these factors should be weighed and reasonably concur to the final decision.