The combination of venetoclax and gilteritinib was associated with high response rates in patients with relapsed or refractory FLT3-mutated acute myeloid leukemia (AML) regardless of prior FLT3 inhibitor exposure, according to results from a phase Ib, open-label, dose-escalation, and dose-expansion study.
The results were published in the Journal of Clinical Oncology in a paper by Naval Daver, MD, of The University of Texas MD Anderson Cancer Center and colleagues.
The study enrolled 61 patients with FLT3 wild-type (n=5) or FLT3-mutated (n=56) relapsed or refractory AML. Of the 56 patients with FLT3-mutated AML, 64% (n=36) had received prior FLT3 inhibitor therapy.
Patients received oral venetoclax 400 mg once daily and oral gilteritinib 80 mg or 120 mg once daily. The primary objectives were safety, identification of the recommended phase II dose, and the modified composite complete response (mCRc) rate (complete response [CR] plus CR with incomplete blood count recovery plus CR with incomplete platelet recovery plus morphologic leukemia-free state) using the ADMIRAL phase III-defined response criteria.
The most common grade 3/4 adverse events were cytopenias (n=49; 80%). Adverse events prompted dose interruptions of venetoclax in 51% of patients and of gilteritinib in 48% of patients.
The mCRc rate for patients with FLT3-mutated AML was 75% (CR, 18%; CR with incomplete blood count recovery, 4%; CR with incomplete platelet recovery, 18%; and morphologic leukemia-free state, 36%) and was similar among patients with or without prior FLT3 inhibitor therapy (80% vs 67%, respectively). The median follow-up was 17.5 months. The median time to response was 0.9 months, and the median remission duration was 4.9 months (95% CI, 3.4-6.6).
FLT3 molecular response (<10-2) was achieved in 60% of evaluable mCRc patients (n=15 of 25). The median overall survival for patients with FLT3-mutated AML was 10 months.
The recommended phase II dose was established as venetoclax 400 mg once daily and gilteritinib 120 mg once daily.
“The combination of venetoclax and gilteritinib was associated with high mCRc and FLT3 molecular response rates regardless of prior FLT3 inhibitor exposure,” Dr. Daver and colleagues wrote. “Dose interruptions were needed to mitigate myelosuppression.”
Daver N, Perl AE, Maly J, et al. Venetoclax plus gilteritinib for FLT3-mutated relapsed/refractory acute myeloid leukemia. J Clin Oncol. 2022;40(35):4048-4059. doi:10.1200/JCO.22.00602