Identifying TKI Resistance in Patients

EP: 1.Current Standards of Care in Patients with Chronic Phase Chronic Myeloid Leukemia (CP-CML) and Philadelphia Chromosome-Positive ALL (Ph+ ALL)

EP: 2.Goals of Treatment for Patients with CP-CML and Acute Phase CML

EP: 3.Factors Impacting CML Treatment Selection

EP: 4.IRIS Trial Highlighting Role of Imatinib in CML Treatment

EP: 5.OPTIC Trial Overview

EP: 6.Unmet Needs Surrounding CP-CML and Ph+ ALL

EP: 7.Effects of TKI Resistance and Intolerance

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EP: 8.Identifying TKI Resistance in Patients

EP: 9.Challenges in Treating Resistant CP-CML or Ph+ ALL

EP: 10.Informed Clinical Decision-Making in CP-CML or Ph+ ALL

EP: 11.Considerations for Second and Third Generation TKI Treatment

EP: 12.Novel Agents as Third-Line Treatment Options

Brandon Dyson, PharmD, BCOP, BCPS: How do we identify TKI [tyrosine kinase inhibitor] resistance in our patients with CML [chronic myeloid leukemia] or Ph [Philadelphia chromosome]-positive ALL [acute lymphoblastic leukemia]? I think, especially with chronic phase CML, we don’t typically do mutational testing up front. If a patient presents with chronic phase CML, there are mutations, most of them are induced, but most of them aren’t present at presentation and are not there in the upfront setting. They occur as almost a response to TKIs. So we don’t do much up front, we just pick the best TKI for that patient, and move forward with it.

When do we start checking? Well, that changes things a bit. I think when patients aren’t meeting their milestones, and again, the NCCN [National Comprehensive Cancer Network] has a nice stoplight color-coded chart of some of these milestones. What it’s looking at is log reductions in BCR-ABL on your PCR [polymerase chain reaction] test, measuring from your blood how much BCR-ABL is present, and at what time points. Because again, we know that the earlier we get the patient to that major molecular response, the better they do. So when a patient has not achieved the 10 log reduction by, say 3 months or 6 months, however it’s spelled out on the NCCN milestones, that can start raising questions. One of the first things you need to do is to ensure that the patient is taking the drug. Adherence is crucial here; it doesn’t matter how effective the drug is if the patient is not taking it. All of that patient conversation, education, and having them be an active participant in their therapy, this is where all of that really matters. That’s the first thing you want to start looking for, ensuring there’s adherence.

But then beyond that, now is probably a good time to start looking for mutations. Because if a patient has a T315I mutation, for example, let’s say we’ve had them on imatinib, in most cases, a logical second-line therapy would be to put them on a second-generation TKI, like dasatinib. But if they have a T315I mutation, they are not a candidate for anything, and so that really determines where we’re going next. It would be an expensive waste of time if we were to transition someone from imatinib to a second-generation TKI if they had the T315I mutation. So we start looking for resistance, we start looking for typing when a patient’s not making their goal, basically, when they’re not hitting their milestones. Or if we see a progression, if we see a loss of control, any of those things are going to tip us off that there’s something going on, and we might want to look at the mutational burden there.

Transcript edted for clarity.