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Observational Study
. 2025 Apr 8;9(7):1544-1554.
doi: 10.1182/bloodadvances.2024014014.

Trial eligibility, treatment patterns, and outcome for venetoclax-based therapy in AML: a prospective cohort study

Ofir Wolach  1   2 , Itai Levi  3 , Boaz Nachmias  4 , Sigal Tavor  5 , Irina Amitai  2   6 , Yishai Ofran  7 , Chezi Ganzel  7 , Tsila Zuckerman  8   9 , Doaa Okasha  10 , Ilana Hellmann  11 , Tamar Tadmor  9   12 , Najib Dally  13 , Jonathan Canaani  14 , Galia Stemer  15 , Moshe Grunspan  16 , Adi Jacob Berger  16 , Neta Frankel  16 , Jenia Berelovich  16 , Alexandra Bleterman  16 , Moran Barak  16 , Raanan Cohen  16 , Yakir Moshe  17
Affiliations
Observational Study

Trial eligibility, treatment patterns, and outcome for venetoclax-based therapy in AML: a prospective cohort study

Ofir Wolach et al. Blood Adv. .

Abstract

Venetoclax plus hypomethylating agents are considered standard of care for patients with acute myeloid leukemia (AML) judged ineligible for intensive chemotherapy (IC). Real-world studies complement clinical trials, because patterns of patient selection, treatment exposure, and postremission management may vary. This prospective observational multicenter study included 209 newly diagnosed IC-ineligible patients with a median age 75 years (interquartile range, 71-81 years). A high proportion of patients had secondary AML (53.7%), adverse-risk disease (35.3%), and complex karyotype (15.5%). At a median follow-up of 22.5 months (range, 0.1-43), median overall survival (mOS) was 11.7 months (95% confidence interval [CI], 9.9,15.4). Composite complete remission was achieved in 65.2% (CR, 44.4%; CR with incomplete hematologic recovery, 20.8%). Of responding patients, 21.1% underwent stem cell transplantation. When stratified based on VIALE-A original eligibility criteria, mOS was 17.8 months for patients meeting eligibility criteria and 10.7 months for patients who did not (P = .027). AML ontogeny (P = .024), reduced kidney function (P = .001), Charlson Comorbidity Index (CCI; P = .0017), European LeukemiaNET (ELN) risk (P = .01), and body mass index (P = .0298) were significantly associated with OS. Multivariant Cox regression analysis confirmed independent association of OS with AML ontogeny (P = .012), CCI (P = .033), and ELN risk (P = .019). Patients enrolled in the latter half of the study period demonstrated improved OS than those enrolled earlier (P = .026). This prospective observational study highlights outcomes of patient subgroups, including those excluded from registration trials. This trial was registered at www.clinicaltrials.gov as #NCT03987958.

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Conflict of interest statement

Conflict-of-interest disclosure: O.W. reports research support from AbbVie; speaker honoraria from AbbVie, Astellas, and Novartis; and an advisory role with AbbVie, Astellas, Novartis, Pfizer, Medison, and Teva. Y.M. reports an advisory role with AbbVie, Astellas, Bristol Myers Squibb, Gilead, Medison, Neopharm, Novartis, and Pfizer; and honoraria from and consultancy with AbbVie, Astellas, Medison, Novartis, and Takeda. B.N. reports speaker honoraria from and consultancy with AbbVie. Y.O., S.T., and G.S. report consultancy with AbbVie. T.T. reports research support from AbbVie. J.C. reports speaker honoraria from and consultancy with AbbVie. M.G., A.J.B., N.F., J.B., A.B., M.B., and R.C. report employment with AbbVie, and may hold stock or other options. The remaining authors declare no competing financial interests.

A complete list of the members of the Israeli Acute Leukemia Working Group appears in “Appendix.”

Figures

None
Graphical abstract
Figure 1.
Figure 1.
CONSORT diagram. A total of 209 patients signed the informed consent; 169 patients discontinued treatment early; of them, 135 died at data cutoff. Seven patients completed the study (reached to cycle 30).
Figure 2.
Figure 2.
Treatment pattern per cycle for patients treated with Ven-Aza. Cycle duration was defined as the number of days between 2 consecutive Aza treatments. Ven duration was defined as Ven treatment days within each Aza cycle. The last cycle for each patient was excluded. Box represent the 25th and 75th quartiles.
Figure 3.
Figure 3.
Overall patient outcomes. The distributions were estimated using the Kaplan-Meier method; tick marks indicate censored data. (A) OS, (B) CRc, and (C) time to first remission (CR/CRi/MLFS/PR); patients without response assessment were censored on day 1. (D) Duration of remission (CR/CRi/MLFS/PR). (E) EFS.
Figure 4.
Figure 4.
Clinical outcome by AML type. The distributions were estimated using the Kaplan-Meier method; tick marks indicate censored data. (A) OS, (B) CRc, and (C) duration of remission.
Figure 5.
Figure 5.
Outcomes of VIALE-A–eligible and VIALE-A–ineligible patients. The distributions were estimated using the Kaplan-Meier method; tick marks indicate censored data. (A) OS, (B) CRc, (C) forest plot showing the mOS for the different ineligibility criteria. CRc was not significantly different between groups (P = .17; χ2 test). Only criteria with >10 patients in each arm were included. Bars represent 95% CI. Missing bars indicate 95% CI NR.
See this image and copyright information in PMC

References

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