OPTI-AML: Prospective Comparison of 28 vs.14 days of Venetoclax Induction with Azacitidine in Older Adults with AML
Abstract
Azacitidine (Aza) plus venetoclax (Ven) is standard treatment for older/unfit patients with newly diagnosed (ND) acute myeloid leukemia (AML). The approved 28-day (D) Ven schedule is associated with prolonged cytopenias, causing frequent dose reductions and cycle delays. Retrospective studies show similar efficacy and reduced toxicity with abbreviated Ven dosing, but prospective data is lacking. We conducted OPTI-AML(NCT03013998), a prospective randomized phase 2 trial comparing 28D Ven (AV28) versus 14D (AV14) with Aza (75mg/m²x7D) for C1-2 in genomically agnostic ND-AML patients ≥60 years. The primary endpoint was complete remission (CR) rate achieved at any time with two cycles of therapy. Between 2023-2025, 169 patients received AV28 (n=83) or AV14 (n=86). CR across two cycles was 49.4% (AV28) versus 43% (AV14); difference of 6.4% [90%CI:-6.1% to 19.0%], not meeting non-inferiority criteria. Patients with NPM1/ IDH2 mutations had higher CR rates with AV28 (60.9% vs. 33.3%), while CR rates were equivalent (45%) for other subgroups. Composite CR rates were 80.7% (AV28) versus 68.6% (AV14) and MRD negativity was similar (77.6% vs. 76.5%). Although AV28 had more frequent treatment interruptions, count recovery after C2, grade ≥3 adverse events and early mortality were similar. In conclusion, the study did not demonstrate non-inferiority of AV14 compared with AV28 during C1-2 in an unselected ND-AML cohort. However, as the confidence interval for the difference covered 0, CR rate for AV28 was not significantly different than AV14. Certain subgroups may benefit from prolonged Ven exposure, but these findings require validation in larger studies, especially as triplet regimens evolve.
Article Details
Authors (37)
Uma M Borate
The Ohio State University, Columbus, Ohio, United States
Ying Huang
Tara L. Lin
University of Kansas, Fairway, Kansas, United States
Shivani Handa
The Ohio State University, Columbus, Ohio, United States
Ronan Swords
OHSU Knight Cancer Institute Center for Hematologic Malignancies, Portland, Oregon, United States
Curtis A. Lachowiez
Oregon Health & Science University, Portland, Oregon, United States
Elie Traer
Oregon Health & Science University, Portland, Oregon, United States
Wendy Stock
Olatoyosi Odenike
University of Chicago Medicine and Comprehensive Cancer Center, Chicago
Anand A Patel
University of Chicago, Chicago, Illinois, United States
Maria R Baer
University of Maryland, Baltimore, Maryland, United States
Vu H. Duong
University of Maryland Greenebaum Comprehensive Cancer Center, Baltimore, Maryland, United States
Eytan M. Stein
Leukemia Service Department of Medicine Memorial Sloan Kettering Cancer Center New York New York USA
William Blum
Emory University, Atlanta, Georgia, United States
Colin Anthony Vale
Emory Univeristy, Atlanta, Georgia, United States
Emily Curran
University of Cincinnati College of Medicine, Cincinnati, Ohio, United States
Yazan F. Madanat
UT Southwestern Medical Center, Dallas, Texas, United States
Rebecca L. Olin
University of California San Francisco, San Francisco, California, United States
Gary J. Schiller
David Geffen School of Medicine at UCLA, Los Angeles, California, United States
Angela D Nichols
University of North Carolina, Chapel Hill, North Carolina, United States
Lacey Williams
University of North Carolina, Chapel Hill, North Carolina, United States
Nyla A. Heerema
Mary F Johnson
MJBiostat LLC, Spring Lake, New Jersey, United States
Timothy L Chen
The Ohio State University, Columbus, Ohio, United States
Sonja Marcus
The Leukemia and Lymphoma Society, Rye Brook, New York, United States
Molly Martycz
The Ohio State University, Columbus, Ohio, United States
Mona Stefanos
OSU, Columbus, Ohio, United States
Leonard Rosenberg
The Leukemia and Lymphoma Society, Rye Brook, New York, United States
Louis James DeGennaro
Blood Cancer United, Washington, District of Columbia, United States
Lore Gruenbaum
Blood Cancer United, Washington, District of Columbia, United States
Amy Burd
The Leukemia and Lymphoma Society, Rye Brook, New York, United States
John C Byrd
UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania, United States
Brian J. Druker
Oregon Health & Science University, Portland, Oregon, United States
Ross L Levine
Memorial Sloan-Kettering Cancer Center, New York, New York, United States
Ashley O Yocum
Blood Cancer United, Washington, District of Columbia, United States
Alice S. Mims
The Ohio State University, Columbus, Ohio, United States
Joshua F Zeidner
University of North Carolina, Lineberger Comprehensive Cancer Center, Chapel Hill, North Carolina, United States