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. 2025 Apr 17;15(1):68.
doi: 10.1038/s41408-025-01269-x.

Reduced venetoclax exposure to 7 days vs standard exposure with hypomethylating agents in newly diagnosed AML patients

Christophe Willekens #  1 , Alexandre Bazinet #  2 , Samy Chraibi  3 , Alex Bataller  2 , Justine Decroocq  4 , Naszrin Arani  2 , Benjamin Carpentier  5 , Caitlin Rausch  2 , Delphine Lebon  6 , Abhishek Maiti  2 , Nicolas Gauthier  7 , Nicholas Short  2 , Sarah Bonnet  8 , Koji Sasaki  2 , Sabine Khalife-Hachem  1 , Mahesh Swaminathan  2 , Jean-Baptiste Micol  1 , Florence Pasquier  1 , Christophe Marzac  9 , Damien Roos-Weil  7 , Laurent Pascal  5 , Naval Daver  2 , Tapan Kadia  2 , Didier Bouscary  4 , Farhad Ravandi  2 , Arnaud Pages  10 , Hagop Kantarjian  2 , Stéphane De Botton  11 , Courtney DiNardo  2
Affiliations

Reduced venetoclax exposure to 7 days vs standard exposure with hypomethylating agents in newly diagnosed AML patients

Christophe Willekens et al. Blood Cancer J. .

Abstract

Hypomethylating agent (HMA) plus venetoclax (VEN) regimens are standard of care in patients with acute myeloid leukemia (AML) ineligible for intensive chemotherapy. While the VEN label recommends continuous 28-day cycles, shortened VEN durations may induce similar response rates and improve tolerability. It is unknown how a VEN exposure reduced to 7 days during cycles compares to standard HMA + VEN. We retrospectively compared newly diagnosed AML patients treated with azacitidine (AZA) x 7 days plus VEN x 7 days ("7 + 7" regimen) from the first cycle (n = 82) vs patients treated with standard dose HMA + VEN (std-HMA/VEN) (n = 166). Composite complete remission rate was similar between cohorts (72% vs 72%; p = 0.95) and a median number of cycles to best response was 2 with "7 + 7" vs 1 with std-HMA/VEN (p = 0.03). Concerning toxicity, platelet transfusion rates during cycle 1 as well as early mortality at 8-weeks (6% vs 16%; p = 0.03) were lower in "7 + 7" cohort. Finally, the median OS was 11.2 months (2-year 28%) with "7 + 7" vs 10.3 months (2-year 34%) with "std-HMA/VEN" (p = 0.75). In summary, acknowledging limitations of a retrospective comparison, a shortened course of VEN used for 7 days every 28 days resulted in similar response rates and survival when compared to standard VEN exposure.

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Conflict of interest statement

Competing interests: CW: Consultant/Advisory Boards: BMS, Abbvie. NG: Consultant/Advisory Boards: BMS. JBM: Honoraria: Jazz Pharmaceuticals, Astellas Pharma, SERVIER. Consultant/Advisory Boards: AbbVie, Gilead Sciences. Travel, Accommodations, Expenses: AbbVie. CM: Research funding: Incyte. LP: Consultant/Advisory Boards: Janssen, Takeda, Abbvie, Gilead, Kephren and Résilience. SDB: Consultant/Advisory Boards: Servier, BMS, GSK, Syndax Pharmaceuticals, and Remix Therapeutics. Honoraria from BMS, AbbVie, Servier, Jazz Pharmaceuticals, Astellas, and Loxo Oncology. Speakers’ bureau: Servier, BMS, Jazz Pharmaceuticals, Astellas, and AbbVie. Research funding: Forma Therapeutics and Auron Therapeutics. CD: Consultant/Advisory Boards: Abbvie, AstraZeneca, Astellas, BMS, Genentech, GenMab, GSK, ImmuneOnc, Notable Labs, Rigel, Schrodinger, Servier. CDD is supported by the LLS Scholar in Clinical Research Award. ABazinet, SC, ABataller, JD, NA, BC, CR, DL, AM, NS, SB, KS, SKH, MS, FP, DRW, ND, TK, DB, FR, AP and HK had no conflict of interest.

Figures

Fig. 1
Fig. 1. Cycles to first and best response by treatment regimen.
A Number of cycles to achieve first response in responders, stratified by treatment regimen. B Number of cycles to achieve best response in responders, stratified by treatment regimen.
Fig. 2
Fig. 2. Overall survival and event-free survival of “7 + 7” vs “std-HMA/VEN” cohorts.
A Overall survival stratified by treatment cohort. B Event-free survival stratified by treatment cohort. EFS event-free survival, HMA hypomethylating agent, OS overall survival, VEN venetoclax.
Fig. 3
Fig. 3. OS and EFS stratified by treatment cohort and mPRS, uncensored for allogeneic SCT.
A Overall survival stratified by treatment cohort and molecular prognostic risk signature (mPRS) predicted benefit (high, intermediate, or low benefit). B Event-free survival stratified by treatment cohort and mPRS. EFS event-free survival, HMA hypomethylating agent, mPRS molecular prognostic risk signature, OS overall survival, SCT stem cell transplant, VEN venetoclax.
Fig. 4
Fig. 4. Univariate and multivariate analysis of OS in whole cohort and cohort with high-benefit predicted by mPRS.
A Univariate and multivariate analysis of overall survival in whole cohort. B Univariate and multivariate analysis of overall survival in patients with a high-benefit predicted by molecular prognostic risk signature (mPRS). AML-pCT AML post-cytotoxic therapy, CG cytogenetic, DAC decitabine, HMA hypomethylating agent, mPRS molecular prognostic risk signature, OS overall survival, PS Performance Status, VEN venetoclax.
See this image and copyright information in PMC

References

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