It may be appropriate to conduct follow-up mutational testing in patients with chronic myeloid leukemia (CML) who have progressed from chronic phase to accelerated or blast phase, lost their hematologic or cytogenetic response, or for those who have had a log fold increase in their BCR-ABL copy number, explains Jessica K. Altman, MD.

Importantly, acquired mutations that cause resistance to imatinib may not impact second-generation inhibitors, like nilotinib and dasatinib. However, acquired T315I mutations result in resistance to most of the approved kinase inhibitors in CML; however, ponatinib is able to overcome this resistance mechanism. Many treatment guidelines provide information on which mutations are problematic for each kinase inhibitor, Altman notes. This information should be used when making treatment decisions.

Stuart L. Goldberg, MD, explains that mutation tests are available to community oncologists and should be ordered, especially when considering a switch to a more expensive second-generation drug. He also discusses the importance of doing the tests while the patient is still on the drug that’s not working, while Neil P. Shah, MD, PhD, describes strategies for working with the laboratories conducting the mutational analyses.