Publication details

Long-term follow-up of VIALE-A: Venetoclax and azacitidine in chemotherapy-ineligible untreated acute myeloid leukemia

Authors	PRATZ Keith W JONAS Brian A PULLARKAT Vinod THIRMAN Michael J GARCIA Jacqueline S DOEHNER Hartmut RECHER Christian FIEDLER Walter YAMAMOTO Kazuhito WANG Jianxiang YOON Sung-Soo WOLACH Ofir YEH Su-Peng LEBER Brian ESTEVE Jordi MAYER Jiří PORKKA Kimmo ILLES Arpad LEMOLI Roberto M TURGUT Mehmet KU Grace MILLER Catherine ZHOU Ying ZHANG Meng CHYLA Brenda POTLURI Jalaja DINARDO Courtney D
Year of publication	2024
Type	Article in Periodical
Magazine / Source	American Journal of Hematology
MU Faculty or unit	Faculty of Medicine
Citation
web	https://onlinelibrary.wiley.com/doi/10.1002/ajh.27246
Doi	http://dx.doi.org/10.1002/ajh.27246
Keywords	acute myeloid leukemia; venetoclax; azacitidine
Description	Venetoclax-azacitidine is approved for treatment of patients with newly diagnosed acute myeloid leukemia (AML) ineligible for intensive chemotherapy based on the interim overall survival (OS) analysis of the VIALE-A study (NCT02993523). Here, long-term follow-up is presented to address survival benefit and long-term outcomes with venetoclax-azacitidine. Patients with newly diagnosed AML who were ineligible for intensive chemotherapy were randomized 2:1 to receive venetoclax-azacitidine or placebo-azacitidine. OS was the primary endpoint; complete remission with/without blood count recovery (CR/CRi) was a key secondary endpoint. This final analysis was conducted when 100% of the predefined 360 OS events occurred. In VIALE-A, 431 patients were enrolled to venetoclax-azacitidine (n = 286) or placebo-azacitidine (n = 145). At 43.2 months median follow-up, median OS was 14.7 months (95% confidence interval [CI], 12.1-18.7) with venetoclax-azacitidine, and 9.6 months (95% CI, 7.4-12.7) with placebo-azacitidine (hazard ratio, 0.58 [95% CI, 0.47-0.72], p < .001); the estimated 24-month OS rate was 37.5% and 16.9%, respectively. Median OS for patients with IDH1/2 mutations and those with measurable residual disease responses was reached in this final analysis. CR/CRi rate was similar to interim analysis. Any-grade hematologic and gastrointestinal adverse events were most common in venetoclax-azacitidine and placebo-azacitidine arms, including thrombocytopenia (47% and 42%) and neutropenia (43% and 29%). No new safety signals were identified. Long-term efficacy and safety confirm venetoclax-azacitidine is an improvement in standard-of-care for patients with AML who are not eligible for intensive chemotherapy because of advanced age or comorbidities.