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Personal Experience Managing AML With Quizartinib

Insights From: Richard F. Schlenk, MD, University of Ulm; Harry Erba, MD PhD, University of Alabama ; Naval G. Daver, MD, MD Anderson Cancer Center
Published: Friday, Oct 12, 2018



Transcript:

Richard F. Schlenk, MD:
I have personal experience in using quizartinib: We participated in the phase II study of patients with relapsed and refractory disease with FLT3 internal tandem duplication [ITD], which was recently published in Lancet Oncology. I remember a 75-year-old patient with a relapsed AML FLT3 internal tandem duplication who could be treated on an outpatient basis, which was really impressive. Following treatment, the patient achieved a complete remission; however, as we know, resistance mechanisms are in place, and in these older patients we are not able to move towards another transplantation. He eventually relapsed after 8 months. But it is important to note that he unexpectedly sustained remission for 8 months, an anomaly for patients in this setting.

Naval G. Daver, MD: I have experience with quizartinib. At MD Anderson, we participated in the phase I quizartinib dose-finding study, which was published in the Journal of Clinical Oncology. One of the interesting findings allowed all relapsed AML; they allowed FLT3-mutated and FLT3–non-mutated patients. Many people, including experts, forget that even in the FLT3–non-mutated group, quizartinib actually has about a 32% marrow remission rate. There have been a lot of preclinical papers showing that although quizartinib is a potent inhibitor of FLT3 ITD-mutated cells, it also has very potent KIT and RAF inhibition. We think that in some AML patients, even those who do not harbor the FLT3 ITD mutation, the inhibition of KIT could be playing a major role, which was one of the key findings of the study.

Additionally, we’ve participated in both phase II studies of quizartinib. There were 2 of these studies, and the first looked at about 180 elderly patients with relapsed AML; the other one observed salvage therapy in younger patients with relapsed AML. What’s unique and interesting about quizartinib has been the response rates across all these studies: the phase I study, the 2 large phase II studies, and the QuANTUM-R phase III study, all of which have been very consistent. This is not something we often see in drug development in leukemia or in other solid tumors. We usually see that the response rates drop off in the phase III trial because in the phase II setting, you have very experienced centers that manage the patients a little better, since they have more leukemia expertise.

When you go to a phase III, you open it to 100 centers, and you have a little bit of drop-off. But with quizartinib, what has been interesting is that the 50% bone marrow remission rates have been very stable in the phase III, phase II, and phase I settings. I believe that even in the community, the response rates will stay between 45% and 50%. This is a realistic expectation, not just what was seen in trials.


Transcript Edited for Clarity
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Transcript:

Richard F. Schlenk, MD:
I have personal experience in using quizartinib: We participated in the phase II study of patients with relapsed and refractory disease with FLT3 internal tandem duplication [ITD], which was recently published in Lancet Oncology. I remember a 75-year-old patient with a relapsed AML FLT3 internal tandem duplication who could be treated on an outpatient basis, which was really impressive. Following treatment, the patient achieved a complete remission; however, as we know, resistance mechanisms are in place, and in these older patients we are not able to move towards another transplantation. He eventually relapsed after 8 months. But it is important to note that he unexpectedly sustained remission for 8 months, an anomaly for patients in this setting.

Naval G. Daver, MD: I have experience with quizartinib. At MD Anderson, we participated in the phase I quizartinib dose-finding study, which was published in the Journal of Clinical Oncology. One of the interesting findings allowed all relapsed AML; they allowed FLT3-mutated and FLT3–non-mutated patients. Many people, including experts, forget that even in the FLT3–non-mutated group, quizartinib actually has about a 32% marrow remission rate. There have been a lot of preclinical papers showing that although quizartinib is a potent inhibitor of FLT3 ITD-mutated cells, it also has very potent KIT and RAF inhibition. We think that in some AML patients, even those who do not harbor the FLT3 ITD mutation, the inhibition of KIT could be playing a major role, which was one of the key findings of the study.

Additionally, we’ve participated in both phase II studies of quizartinib. There were 2 of these studies, and the first looked at about 180 elderly patients with relapsed AML; the other one observed salvage therapy in younger patients with relapsed AML. What’s unique and interesting about quizartinib has been the response rates across all these studies: the phase I study, the 2 large phase II studies, and the QuANTUM-R phase III study, all of which have been very consistent. This is not something we often see in drug development in leukemia or in other solid tumors. We usually see that the response rates drop off in the phase III trial because in the phase II setting, you have very experienced centers that manage the patients a little better, since they have more leukemia expertise.

When you go to a phase III, you open it to 100 centers, and you have a little bit of drop-off. But with quizartinib, what has been interesting is that the 50% bone marrow remission rates have been very stable in the phase III, phase II, and phase I settings. I believe that even in the community, the response rates will stay between 45% and 50%. This is a realistic expectation, not just what was seen in trials.


Transcript Edited for Clarity
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