BCR-ABL1 TKIs in Relapsed/Refractory CML - Episode 4

Importance of Compliance With TKIs in Treatment of CML

June 24, 2019

Harry Erba, MD, PhD:I see patients referred to me for apparent loss of response or resistance. This is typically based on these variations in theBCR-ABLratio. Your group has published exactly how much of a change do you need to see for it to actually be worrisome. If you could comment on that, and then we could talk about what you do at that point if you’d see a real change.

Jorge Cortes, MD:I think that’s a very important point because the PCR [polymerase chain reaction], as good as it is and as sensitive as it is, has variability just like any other blood test that we do here in our view. If you run a test twice on the same patient on a given day, you may find slightly different abnormalities. We know that the coefficient of variability on a PCR—in a good laboratory, there’s nothing wrong with the technique or anything—could be half a log or even higher than that. These small changes, they don’t have to trigger anything. If you have concerns, you may want to even check it again before you do any big changes. If it’s more than a log difference, let’s say somebody goes from 0.1% to 1%, well, that seems to be more than the coefficient of variability on the test. But even then, I always repeat it because you never know if there is a technical error or anything like that. Fortunately, those patients are clinically OK. You can wait a few weeks to get another test and wait for the results. It’s only blood, so it’s also not that inconvenient for the patients. I think it is always important to confirm and to accept that there is some variability with the test.

Harry Erba, MD, PhD:One of the things I do is, I agree with your comments and really take guidance from the work that you’ve done at The University of Texas MD Anderson Cancer Center on this point, but I do think it’s important to give that information back to the patient. If we see it go from 0.1% to 0.2%, I think you and I won’t freak out about that. But if you tell the patient that, they might be a little bit more compliant with their therapy. They might say, “Oh, I missed a few doses and they’re seeing it, and I’m worried.” What do you think?

Jorge Cortes, MD:Absolutely….The patients, when you see them in the clinic, don’t have the results. They usually communicate the results with you later on. When you get those results, the first thing I ask them is precisely that. I say, “Have you missed any doses?” Because that’s the most common reason why you would see such a small increase. It’s important the patient recognizes that even a few doses can have such an impact, particularly important that they recognize that when it’s a little change and not when it could be something a lot more meaningful to them. I fully agree that that’s an important feedback for the patient.

Harry Erba, MD, PhD:Yes, it’s quite amazing, actually. Some of the adherence studies have shown as much as a 10% noncompliance can actually affect your ability to meet milestones.

Jorge Cortes, MD:That is important. Because if you think about it, 10% missed doses in a month means you missed 3 doses. That doesn’t sound that much when you say, “Well, I just missed probably 3 or 4 doses.” That already reflects into a very low probability of getting to these deeper molecular responses. Particularly for a patient who wants to think about treatment discontinuation and all that, maybe it makes a difference.

Transcript edited for clarity.