Naval Daver, MD

Studying MDM2 inhibitors using Venetoclax (Venclexta) has led to unique responses in patients with acute myeloid leukemia (AML) and warrants wider and further study, according to data presented at the 2019 American Society of Hematology Annual Meeting.

 MDM2 is a gene often associated with overexpression that leads to risk and AML. Researchers from the MD Anderson Cancer Center, in Houston, TX, found that using Venclexta as an inhibitor of MDM2 led to unheard-of responses in this patient group, according to Dr. Naval Daver.

Daver, an associate professor in the department of leukemia at the MD Anderson Cancer Center in Houston, TX, had the chance to sit down with CURE and discuss the results of this study and why it is meaningful for patients with AML.    

At our lab, Dr. Andrea and others in our group have extensively worked on the MDM2 pathway for the last 20 years. We have also done a number of novel combinations with both of these in cell lines, as well as, in xenograft mouse models.

We found a very high synergy with the MDM2 inhibitors with Venetoclax, which is one of the topics we will be presenting here, but also MDM2 inhibitors with the second generation FLT3 inhibitors, both quizartinib and gilteritinib.

So that was the preclinical rationale. We in fact saw mouse survivals that were maintained at more than a hundred days, which is almost unheard of in acute myeloid leukemia relapse studies. So, we think that the preclinical synergy could be very, very, very exciting and that has led to this phase one study. The study will be a global study, it will have about 40 centers across the world.

It is a phase one B study, so the first part is to identify the optimal safe dose and then it will expand in two cohorts, one in relapsed FLT3 ITD mutated patients and one in elderly frontline FLT3 ITD patients. And of course, the goal is to see if we can improve not only response rate, but more importantly, duration of response and survival with the combination as compared to single agent FLT3 inhibitor therapies which have recently been approved.

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Naval Daver, MD

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