The triplet combination of azacitidine, venetoclax, and gilteritinib induced high response rates in patients with newly diagnosed or relapsed/refractory FLT3-mutated acute myeloid leukemia (AML) in a phase 1/2 study.


Patients with relapsed/refractory FLT3-mutated AML (N=20) or newly diagnosed FLT3-mutated AML, unfit for intensive chemotherapy (N=27), received a regimen of azacitidine, venetoclax, and gilteritinib (80 or 120 mg, once daily) in a phase 1/2 study. After the phase 1 part of the study, 80 mg was selected as the phase 2 expansion dose. The primary endpoint of the phase 2 part of the trial was complete remission (CR)/complete remission with incomplete count recovery (CRi). Dr. Nicholas Short (University of Texas) presented the results1 at the 2022 annual meeting of the American Society of Hematology.

CR was achieved in 92% of participants who were treated with the triplet regimen in the frontline. The two remaining patients in this cohort achieved CRi and a morphologic leukemia-free state (MLFS) response, respectively. Correspondingly, 20% of participants in the relapsed/refractory cohort reached CR, 15% achieved CRi, and 35% had an MLFS response. In addition, 93% of participants in the frontline cohort were on marrow remission after 14 days or had an aplastic marrow. In the relapsed/refractory cohort, the corresponding rate was 63%.

“In the frontline cohort, the regimen was generally well tolerated, with minimal non-hematological toxicity,” said Dr. Short. Nonetheless, one patient died due to an infection in this cohort. “In the relapsed/refractory cohort, most adverse events were related to myelosuppression, but mostly manageable with mitigation strategies.” In this cohort, there were four unsteady deaths, including two due to an infection, one because of an intercranial hemorrhage, and one due to disseminated intravascular coagulation.

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