Gemtuzumab for AML

Harry Paul Erba, MD, PhD: Let me, for the sake of time, move on and turn it to gemtuzumab. How do you use gemtuzumab? In June the FDA approved gemtuzumab for pediatric AML [acute myeloid leukemia].

Amir Fathi, MD: I didn’t know that. Thank you. I should know that, but I didn’t know that.

Harry Paul Erba, MD, PhD: It was just today.

Amir Fathi, MD: I can’t comment on that, but the answer to your question is that I use gemtuzumab sparingly. The scenario in which I definitively do use it is in patients who have core binding factor AML and who are younger. We know you generally combine that with chemotherapy. One of the challenges with that of course is getting those results back, so you have time enough to incorporate the treatment. But I do use gemtuzumab in that setting. I also use it in consolidation as well in an effort to cure them. In other scenarios, I have not used it in older patients as single therapy. I know it’s approved for use in that setting. I have not used it in intermediate-risk AML.

I have used it a handful of times for relapsed/refractory disease when I don’t have anything else. I have nothing against gemtuzumab, but it’s not the easiest agent to give. There are infusional reactions in patients who have relapsed disease. You have to worry about the history of transplant. You can dose at a lower dose and decrease that risk, but you’ve still got risk. And I’ll be honest with you, the rates of remission, rate of response is very modest, with a high potential for toxicity in certain patients. So my use of gemtuzumab is very low.

Harry Paul Erba, MD, PhD: The other place you haven’t mentioned, I’m sure you’ve probably used it here, would be the high-risk APL [acute promyelocytic leukemia] patient. Instead of using an anthracycline, using a single dose of gemtuzumab for a count reduction.

Amir Fathi, MD: We’ve used it.

Harry Paul Erba, MD, PhD: It’s hard to get around the meta-analysis showing a survival benefit of gemtuzumab when added to chemotherapy. We’re talking over 3300 patients, a subset with core binding factor [CBF] leukemia is clearly doing better. Some have argued that they didn’t do so well with just chemotherapy, but actually core binding factor leukemias, the overall survival is only around 50% to 60% at best without gemtuzumab. In that study, in that meta-analysis, it was in the 75% range. I think there’s something there.

Gail J. Roboz, MD: I actually have been surprised by the seeming lack of knowledge about those particular data. I guess CBF leukemias are rare. People may not see them much, but it’s important to emphasize on a call like this that those are resoundingly positive data. Most of us view the addition of gemtuzumab in the CBF, the core binding factor leukemia scenario, as in fact standard of care. I still get consults for transplant, consults for all kinds of things for CBF patients who have not received those. In particular, when core binding factor leukemias are combined with many other cytogenetic abnormalities and/or a FLT3 mutation, which are scenarios that happen, those are the particularly confusing ones that then result in, well, does this patient need a transplant? Does this patient need this, that, or the other?

I think we want to keep it pretty pure. If you have a core binding factor patient with or without other cytogenetic abnormalities, with or without FLT3, you probably do have a good shot of curing that patient with chemotherapy and gemtuzumab without doing a transplant and without switching that patient. We’re asked very frequently, should that patient get 7+3 and midostaurin, or 7+3 and gemtuzumab, or 7+3 and both of those drugs? Mark is here, but I believe the best answer to that is to focus on the core binding factor and not on the FLT3 in those patients.

Mark J. Levis, MD, PhD: We get our FISH [fluorescence in situ hybridization] back for core binding factor within hours, so the GO, gemtuzumab ozogamicin, is already hanging before we know the FLT3 status. Our usual decision is they’ve had 7+3, they’ve had GO [gemtuzumab ozogamicin], and they say, “What do we do with the FLT3?” And we often throw it on if the patient is still talking to us.

Gail J. Roboz, MD: I actually think people are much more—it’s somehow much more prominent in their mind to be looking for the FLT3 than to be looking for the STAT FISH [fluorescence in situ hybridization].

Mark J. Levis, MD, PhD: Our algorithm is find that core binding factor fast.

Gail J. Roboz, MD: We have to emphasize that point, that these are your curable patients. These are the ones you want to call.

Mark J. Levis, MD, PhD: Some of your neighbors up there don’t do that, Gail.

Harry Paul Erba, MD, PhD: I moved to the Duke University School of Medicine 2 years ago and I’ve taken a little heat for giving GO [gemtuzumab ozogamicin] to the CBF patients as opposed to giving midostaurin alone to those patients if they’re FLT3 positive. But they’re getting used to me, and I’m hoping they’re not going to kick me out. I kind of like Durham, North Carolina. It’s beautiful here.

Transcript Edited for Clarity