Impact of FLT3 mutation on outcomes after venetoclax and azacitidine for patients with treatment-naive acute myeloid leukemia
- Author(s)
- Konopleva, M; Thirman, MJ; Pratz, KW; Garcia, JS; Recher, C; Pullarkat, V; Kantarjian, HM; DiNardo, CD; Dail, M; Duan, Y; Chyla, B; Potluri, J; Miller, CL; Wei, AH;
- Journal Title
- Clinical Cancer Research
- Publication Type
- epub ahead of print
- Abstract
- PURPOSE: Evaluate efficacy and safety of venetoclax+azacitidine among treatment-naïve patients with FLT3 mutant acute myeloid leukemia. PATIENTS AND METHODS: Data were pooled from patients enrolled in a Phase 3 study (NCT02993523) that compared patients treated with venetoclax+azacitidine or placebo+azacitidine and a prior Phase 1b study (NCT02203773) where patients were treated with venetoclax+azacitidine. Enrolled patients were ineligible for intensive therapy due to age {greater than or equal to}75 years and/or co-morbidities. Patients on venetoclax+azacitidine received Ven 400 mg orally (days 1-28) and azacitidine (75 mg/m2; days 1-7/28-day cycle). FLT3 mutation was analyzed centrally on pretreatment bone marrow aspirates. RESULTS: In the biomarker evaluable population, FLT3 mutation was detected in 42 (15%) and 22 (19%) patients in the venetoclax+azacitidine and azacitidine groups. Composite complete remission (CRc, complete remission [CR]+CR with incomplete hematologic recovery [CRi]) rates (venetoclax+azacitidine /azacitidine) for FLT3 mutant patients were 67%/36%, median duration of remission (DoR) was 17.3/5.0 months, and median OS was 12.5/8.6 months. The CRc rates among FLT3 wild-type were 67%/25%, median DoR 18.4/13.4 months, and median OS 14.7/10.1 months. In patients treated with venetoclax+azacitidine, CRc in patients with FLT3-ITD and FLT3-TKD was 63% and 77%, median OS was 9.9 and 19.2 months, and in co-mutated FLT3-ITD+NPM1, CRc was 70%, median DoR was not reached, and median OS was 9.1 months. There were no unexpected toxicities in the venetoclax+azacitidine group. CONCLUSION: When treated with venetoclax+azacitidine, patients with FLT3 mutations and FLT3 wild-type had similar outcomes. Future analyses in larger patient populations may further define the impact of venetoclax+azacitidine in patients harboring FLT3-ITD.
- Research Division(s)
- Blood Cells And Blood Cancer
- PubMed ID
- 35063965
- Publisher's Version
- https://doi.org/10.1158/1078-0432.Ccr-21-3405
- Open Access at Publisher's Site
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Creation Date: 2022-02-18 11:34:25
Last Modified: 2022-02-18 03:13:10