CML: Factors in Selecting a BCR-ABL TKI

Transcript:

Harry P. Erba, MD: Can I bring up something really controversial, though? And that is, what are your feelings about the doses and schedules of the 4 drugs? I know that’s very controversial, but a lot has been said about food restrictions and once versus twice daily dosing. How important is that? Is that the end of the discussion for you or just part of the discussion?

Michael Mauro, MD: That has got to be the last thing in my mind. I think you need to have the proper education of patient and the risk of serious disease with potential major consequence with fantastic treatment options. So, yes, there are different requirements and different schedules. And we know that on adherence, it can be difficult. But I definitely issue the notion that that should be sort of the first consideration. Like this is a good drug for a patient because they need a convenient once-daily drug. I think whatever is suitable for the patient and then you sort of fit that schedule to the patient. Of course, they may not make it, and you may need to modify based on that. But that’s where the dialog in the clinic, between nursing and clinical staff and the physician, and managing side effects, is going to hopefully carry the day. And, again, that can maybe be the last consideration. I don’t know how.

Jorge E. Cortes, MD: Yes, I agree with you. I think that sometimes we tend to be a little too paternalist with our patients. I know I’m not going to do a bone marrow diagnosis because it hurts, and I’m not going to use this drug because the schedule is difficult. I’m not going to do this and that. That’s not our choice; that’s the patient’s choice. I think our job is to explain why, to explain the benefits, the disadvantages, and maybe even help them explain, you know?

If you just say, “Well, this one is twice a day and you have to maybe not eat and whatever,” it may sound difficult for the patient. What I do is tell them, “Here’s a way that you do it. You wake up first thing in the morning and you take your pill. You’ve already had the fasting, so you don’t have to worry about that. And then by the time you get to eat your breakfast, you’ve already eaten another hour.” So, if you help them to understand how they can incorporate it, that’s an example of the schedule. But you can help the patients understand the significance, why it is important, why you’re using that drug or that test, whatever, and help them navigate through that.

I think in most instances, we get patients to buy into that. It’s a problem when you don’t explain the things. It’s like, if you have to tell a patient that they’re going to get chemotherapy and never tell them they’re going to lose their hair, it’s a much bigger shock than if you told them already. Not that they like it, but at least they’re prepared, they know how to do it. Some will get a wig, some will shave their head, whatever, but you need to explain.

Harry P. Erba, MD: So, along those lines, my experience has been exactly as you’re saying. Not only from the patient perspective but also from the patient’s other physicians. So, when I talk to the patient, they usually say to me, “I understand these are different drugs. I want you to talk to me about what’s the best drug for me, and I’ll figure out with you how to take it.” So, explaining how to get the drug into their lifestyle.

Likewise, when I talk to the internist taking care of other complicated patients, they basically remind me of my job. My job is to take care of the disease, the leukemia, warn them about toxicities, and form a partnership with them to manage those toxicities, whatever they might me. And so, it shouldn’t be specific toxicities and dosing schedules; it should not be the beginning and the end of the discussion. It’s all part of the discussion. We need to learn how to manage these things.

So, if I might ask, then, I guess I kind of heard from both of you that—I’m going to put words in your mouth—if you had your druthers, you think many patients would benefit from a second-generation TKI. But we all still use imatinib. Whom are you using imatinib in? Can you help people with that decision? Is there a prototypical patient? What are some of the issues that come up for you that make you choose imatinib over a second-generation drug? I didn’t say this would be easy today.

Jorge E. Cortes, MD: Yes, well, I think that one important thing—and I’m very careful when I talk about these things, and in particular when I go in other countries and talk about these—I always emphasize that imatinib is a good drug. And that you can treat your patient very well with imatinib if you monitor them properly and you identify the patients who are doing well and the ones who are not doing well because, let’s face it, in the world, the overwhelming majority of the patients are going to be treated with imatinib. And hopefully, they have access to at least imatinib, and that can save many, many lives. So, we shouldn’t forget that it is a good drug.

The other extreme of my statement is that if I have CML and I come to you, please give me a second-generation TKI; that’s what I want. I do value the faster and the deeper responses, a better chance of getting to a sustained MR4.5 or the lower risk of transformation. And yes, I know that imatinib is already low, but for that, I like lower better than low. So, I like that. But then there’s a whole spectrum in between. And I think that we, again, have to individualize these choices.

And I’m not going to get into the third-party payer who forces you to use this or that because that’s unfortunate and there’s nothing we can control over that. But, for example—and I think we’re going to talk a little bit later about some of the risks, and particularly if there are thrombotic events and whatever—it does appear that imatinib has a lesser risk of the 2 thrombotic events.

So, a patient who has a strong history of risk factors and recent MIs and stuff like that, I think imatinib perhaps is the safer drug for that kind of patient. That is 1 scenario where I currently do use imatinib. So, there are going to be some specific scenarios for having all the choices; I still may want to use imatinib. I think that in most instances, I still prefer a second-generation TKI. But there’s a certain patient scenario where I’d use it.

Harry P. Erba, MD: Mike?

Michael Mauro, MD: I think it’s a result of a good discussion. In your mind, you’re going to potentially be steering a patient toward one drug or another, but I think some people just hear about side effects and may have lower-risk disease, although I don’t agree fully with the fact that it’s not just that high-risk patients benefit from more therapy. And I’m really glad that 15-plus years later, imatinib is sort of still going, still at it. And that we even have data; how could we best use imatinib? Not that it’s the right drug for all patients for the long haul, but it may still be a good starting choice.

One example would be data from the TIDEL trials from Australia, where you really can potentially optimize imatinib. You can quickly decide who needs to move on, who needs to go to a second-generation drug; nilotinib maybe after high-dose imatinib, some of the early iterations. But in the end, I think that with several years of follow-up, intermediate-dose imatinib or optimized imatinib can perform basically as well with most people from that trial still being on imatinib—sort of like a two-thirds, one-third ratio of imatinib versus patients moving on to nilotinib. So, you could potentially triage, but that requires very careful, early risk assessment and meticulous switching, and that can’t always happen. So, I think we’re able to maybe overcome a little bit of that lack of capacity sometimes by taking advantage of those benefits from a second-generation inhibitor in a larger group of patients. It was tricky, but I think those were my thoughts.

Transcript Edited for Clarity