Relapsed vs. Refractory Data for FLT3 Inhibitors in AML

Transcript:

Harry Erba, MD, PhD: How about in the relapsed/refractory setting, any difference there—relapsed versus refractory?

Jorge E. Cortes, MD: There was equal benefit in…keep in mind all the relapses were within 6 months. So those patients are not too different from the refractory patients. But we did an analysis by different subsets. And the difference is very similar. The difference in favor of quizartinib is very similar for the 2 subsets.

Harry Erba, MD, PhD: And how about gilteritinib?

Alexander E. Perl, MD, MS: This was one area that if anything, if there was 1 odd person out in terms of which subgroup showed less benefit from gilteritinib versus chemotherapy, the primary refractory was pretty much a wash. It had a similar survival to the chemotherapy, and whether that’s just the design of the study is a little hard to state, because if we looked at the response rates, they were higher in gilteritinib. The median survival was higher in gilteritinib, but the curves crossed, so statistically there was no difference.

Jorge E. Cortes, MD: And we need to keep in mind, when you get to that detail, it’s a small subset. So it’s hard to tell what those things mean.

Alexander E. Perl, MD, MS: At the same time some of these patients may not have had intensive therapy before, so they could have benefited more from the more intensive therapy.

Eunice Wang, MD: I had a question regarding…we have talked about the RATIFY results. So a question that has come up is for both of these trials how many of the patients who are on these trials had gotten a prior 7+3 [cytarabine/daunorubicin] midostaurin? Because that is now the standard of care. So if you have a patient who relapses in this day and age and they’ve gotten that upfront, how many of the patients on both of these trials were exposed to prior midostaurin that we would be able to predict that they would respond now to these second-line agents?

Jorge E. Cortes, MD: In QuANTUM-R, the study was amended after the approval of midostaurin to allow those patients, but it was late into the study, so there was a handful of patients. So there’s not enough data to show what it would do. Obviously, it’s an important question. It’s a more potent inhibitor. Now, quizartinib is a type 2 versus midostaurin, which is a type 1. So I would predict that some patients would still benefit. It is possible that the response rate may be a little bit lower. But today, if I had the quizartinib that I could just prescribe, would I use it? Absolutely. Would I use gilteritinib? Absolutely. But we don’t have a full set of data….

Eunice Wang, MD: OK.

Harry Erba, MD, PhD: I’m going to then say something controversial if you don’t mind. Go figure. And I will say I have been a consultant to the sponsors of both of these drugs. But, as a clinician, I like it that my patients with hypertension can get one of many different beta blockers or ACE [angiotensin-converting enzyme] inhibitors. And the idea that 1 drug in a class is enough just blows my mind. We have 2 studies where patients gave their lives and their trust, went on the study, and both studies met the primary endpoint with acceptable safety. I think there’s room for both drugs to be available to patients, so that we can treat more patients and figure out how to use both drugs in combination to improve on the dismal ultimate outcome of these patients.

Alexander E. Perl, MD, MS: I think that really has to be emphasized because in many ways, we can point out the little differences here, this population had this mutation and that mutation, whether it was 6 months or more than 6 months. But at the end of the day, these are really high-risk patients who need better therapies and easier therapies. And to my eyes, I agree, I think these both achieve the goal, which is we see a high rate of response that’s higher than existing therapies. They do so with really limited toxicity. Patients feel good on these therapies, and if they need to get to transplant, they get there. They get there with greater frequency than available therapies. And I like having that availability to look at 1 drug versus another. And there are potentially even some advantages of quizartinib over gilteritinib in terms of the speed of response, which looks a little bit faster. If you need to get a patient to transplant, that might be a little bit faster way to do it.

Jorge E. Cortes, MD: I agree. As Sasha [Alexander] mentioned, there’s little details here and there. But the bottom line, these are 2 very good drugs, both of them showed the benefit that you would expect, that we all believed we would see, and we saw. We need these 2 drugs.

Harry Erba, MD, PhD: The only curative option for these patients is allogeneic transplant, hopefully with a FLT3 inhibitor as a maintenance afterward. Thirty-six percent of patients on the QuANTUM-R study went on to transplant, 24% on the ADMIRAL trial after those FLT3 inhibitors. These are important drugs to have for our patients, and hopefully we have now 1, and hopefully we’ll have 2 and maybe a third, but I don’t have time to ask you about crenolanib.

Eunice Wang, MD: I totally agree. We need more. We have so many BCR-ABL inhibitors, why can’t we have more than one FLT3 inhibitor?

Jorge E. Cortes, MD: Absolutely.

Harry Erba, MD, PhD: Exactly.

Jorge E. Cortes, MD: This is a worse disease than CML [chronic myeloid leukemia].

Eunice Wang, MD: It’s much worse, yes.

Jorge E. Cortes, MD: Yet we value those in CML.

Transcript Edited for Clarity