(037) Comparing a Reduced Venetoclax Duration Schema to Conventional Dosing Schema in Patients with Treatment Naïve Acute Myeloid Leukemia

Poster Abstract: Background/rationale: Based on results from the VIALE-A trial, the addition of venetoclax (VEN) onto azacitidine (AZA) showed improved overall survival (OS) in treatment naïve acute myeloid leukemia (AML) patients unfit for intensive chemotherapy and now has become the standard of care for these patients. (1,2) A hypomethylating agent (HMA) + VEN has also been verified in various community settings, where they found similar results of longer median OS. (3,4) Though VEN has proven strong efficacy in these patients, high occurrences of cytopenias and febrile neutropenia have been reported which has caused a significant amount of dose changes/modifications to the VEN schedule. (1,3) In addition, these delays didn’t negatively affect efficacy outcomes. Various retrospective studies have also shown no differences in OS, median progression free survival (PFS), median duration of treatment-free remission with similar response rates and less febrile neutropenia events when reducing VEN dosing from the traditional 28-day duration to 7-14 days instead. (5-8) In particular, achieving a complete response (CR) after cycle 1 was the only predictor for a better treatment-free remission. (8) It has also been shown that quality of life increases with subsequent cycles and so ensuring patients remain on therapy while mitigating adverse effects is crucial. (9-10)

Objectives: The primary goal of this study is to compare 2-year survival rates for patients who received < 28 days of VEN vs 28 days of VEN per cycle starting cycle 2 in treatment naïve AML patients who achieved CR or complete response with incomplete hematological recovery (CRi) in combination with a HMA agent such as azacitidine or decitabine.

Methods: This is a retrospective cohort study of all adult Kaiser Permanente Northern California (KP NCAL) members treated with HMA/VEN for their induction cycle from 1/1/2019 – 12/31/2021. Patients will be categorized based on treatment intent by the number of days VEN prescribed after achieving CR or CRi and then followed until their time to event (death, disease progression, etc.). Additional data that will be collected are background characteristics and safety adverse events (occurrences of cytopenias, febrile neutropenia, hospitalizations, and transfusions).

Results: Results pending.

Conclusions/discussion: Not available, pending results.

References (must also be included in final poster): 1. DiNardo CD, Jonas BA, Pullarkat V, et al. Azacitidine and Venetoclax in Previously Untreated Acute Myeloid Leukemia. N Engl J Med. 2020;383(7):617-629. doi:10.1056/NEJMoa2012971
2. National Comprehensive Cancer Network. Acute Myeloid Leukemia (Version 4.2023). https://www.nccn.org/professionals/physician_gls/pdf/aml.pdf. Accessed August 11, 2023.
3. Vachhani P, Flahavan EM, Xu T, et al. Venetoclax and Hypomethylating Agents as First-line Treatment in Newly Diagnosed Patients with AML in a Predominately Community Setting in the US. Oncologist. 2022;27(11):907-918. doi:10.1093/oncolo/oyac135
4. Gershon A, Ma E, Xu T, et al. Early Real-World First-Line Treatment With Venetoclax Plus HMAs Versus HMA Monotherapy Among Patients With AML in a Predominately US Community Setting. Clin Lymphoma Myeloma Leuk. 2023;23(5):e222-e231. doi:10.1016/j.clml.2023.02.002
5. Aiba M, Shigematsu A, Suzuki T, Miyagishima T. Shorter duration of venetoclax administration to 14 days has same efficacy and better safety profile in treatment of acute myeloid leukemia. Ann Hematol. 2023;102(3):541-546. doi:10.1007/s00277-023-05102-y
6. Willekens C, Chraibi S, Decroocq J, et al. Reduced Venetoclax Exposition to Seven Days of Azacitidine Is Efficient in Treatment-Naïve Patients with Acute Myeloid Leukemia. Blood (2022) 140 (Supplement 1): 537–538. doi.org/10.1182/blood-2022-165464
7. Boisclair S, Zhou E, Naing P, et al. Outcomes with Venetoclax Dose De-Escalation and Variable Cycle Intervals: A Real-World AML Survival Analysis. Blood (2022) 140 (Supplement 1): 9023–9024. doi.org/10.1182/blood-2022-169966
8. Garciaz S, Decroocq J, Bertoli S, et al. Long-Term Survival of Acute Myeloid Leukemia Responding Patients Who Stopped Azacytidine and/or Venetoclax Because of Poor Tolerance or Physician Choice: A Retrospective Multicenter Study from the FrenchInnovative Leukemia Organization (FILO). Blood (2022) 140 (Supplement 1): 6147–6148. doi.org/10.1182/blood-2022-158247
9. Chan Y, Richardson D, Berry C, et al. Changes in Symptoms, Function, and Quality of Life in Older Adults with Acute Myeloid Leukemia Treated with Venetoclax and Hypomethylating Agents. Blood (2022) 140 (Supplement 1): 9074–9075. https://doi.org/10.1182/blood-2022-166419
10. Pratz KW, Panayiotidis P, Recher C, et al. Venetoclax combinations delay the time to deterioration of HRQoL in unfit patients with acute myeloid leukemia. Blood Cancer J. 2022;12(4):71. Published 2022 Apr 20. doi:10.1038/s41408-022-00668-8