Evaluating Data From QuANTUM-R: Quizartinib in AML

Transcript:

Richard F. Schlenk, MD: The QuANTUM-R study is a study of patients who have relapsed/refractory acute myeloid leukemia, which invariably follows a dismal prognosis; however, in the QuANTUM-R study, this was even more dismal because they selected patients with refractory disease and 6-month relapse.

Those patients were randomized up front to either single-agent quizartinib or doctor’s choice, which was either intensive chemotherapy, lower intensity chemotherapy, or hypomethylating agents. Most of the patients who were randomized into the doctor’s choice arm received intensive chemotherapy. The randomization was 2-to-1; 2 parts quizartinib, 1 part to doctor’s choice. The results were shown at the European Hematology Association meeting this year and clearly showed that overall survival is improved by single-agent quizartinib, which was given once daily until complete remission was achieved.

The implication of the QuANTUM-R study is that quizartinib will be available for the bridge to transplant in patients with refractory/relapsed disease, because without transplantation—even if the patients achieve a complete remission with single-agent quizartinib—they will shortly relapse thereafter if there is no consolidation therapy with, for example, allogeneic transplantation.

The QuANTUM-R study yielded an improvement in overall survival for patients taking quizartinib; however, so far, the results have not been reported in detail because we do not know the complete remission rate. But if we see a benefit in overall survival, I think this qualifies as a very important study.

In the relapsed/refractory setting of patients with an FLT3 internal tandem duplication, we can clearly see a benefit in overall survival; consequently, I believe quizartinib should be the first choice in such a circumstance. The question is whether quizartinib can be combined with a variety of chemotherapy treatments.

We know from historical data that patients with an FLT3 internal tandem duplication who relapsed, or who were refractory and relapsed within 6 months, did poorly. The overall survival after 1 year is below 20% in historical controls. Therefore, it’s important to see that a single agent, an FLT3 inhibitor such as quizartinib, can induce responses and prolong overall survival. This is really a step forward for these patients in the setting of early relapse and refractory disease.

The safety profile of observed patients in the QuANTUM-R study was very good. The most common toxicity was a QTc prolongation; however, if they are regularly controlled and the QTc time is below 500 milliseconds, then quizartinib is well tolerated.

Transcript Edited for Clarity