Outcomes of Acute Myeloid Leukemia Treated with a Hypomethylating Agent and Venetoclax: A Single Institution Analysis
Authors: Zimmer Markie , Jacob Brigid , Spica Mikayla , Ghosh Sunita , Dabak Vrushali S. 
Published: December 2024

Introduction:
Acute myeloid leukemia (AML) commonly occurs in older adults where intensive therapy is often not well tolerated or as effective. Azacitidine (AZA) and venetoclax (VEN) showed benefit in VIALE-A compared to AZA alone in untreated patients with AML who were ineligible for intensive therapy, with an overall survival (OS) of 14.7 months. Cytopenia, febrile neutropenia and tumor lysis syndrome (TLS) were among the most reported adverse events (DiNardo, 2020).
Methods:
This was a retrospective, single institution analysis of patients over 18 years of age with diagnosis of AML treated with hypomethylating agents (azacitidine or decitabine) (HMA) and VEN between January 2017 and January 2024. We investigate the use of HMA and VEN, trends of regimen and prophylactic regimen dosing, the impact on OS, the use of allo-HSCT and outcomes of relapsed and refractory disease.
Results:
Thirty patients received VEN and HMA for AML between January 2017 and January 2024. Ten patients were female and 20 were male. The median age was 72 years. Twenty-four patients (80%) were Caucasian, 5 (16.7%) were African American and one patient's race was unidentifiable. Twenty-three patients (76.7%) were diagnosed with AML, 5 (16.7%) treatment related AML (t-AML) and 2 (6.7%) MDS/AML. Risk stratifying patients with molecular data available for review by ELN 2022 criteria, there were 5 (16.7%) favorable, 6 (20%) intermediate and 17 (56.7%) adverse. Within the adverse risk group, 6 had mutated TP53.
The median time from diagnostic bone marrow biopsy (BMB) to the start of cycle 1 (C1) was 10.5 days and median time from the start of C1 to the next BMB was 27 days. Patients completed a mean of 5.97 cycles (range, 1-26). Antimicrobial and TLS prophylaxis were used in most patients in C1. VEN duration decreased throughout each cycle (21.60 days in C1, to 15.38 in C2, to 8.62 in C3 and 8.10 in C4). The median number of days between the start of subsequent cycles generally increased (34.5 days from C1 to C2; 39 days from C2 to C3; 42 days from C3 to C4). Twenty-one patients received the treatment in the front-line setting, 7 as salvage therapy and 2 as salvage after allo-HSCT. Three patients proceeded to allo-HSCT a median of 179 days after initial diagnosis.
At data collection, 9 patients (30%) were in remission, 20 (66.7%) had active disease and one patient's disease status was unknown. Mean OS was 22.67 months (5.92-39.42, 95% CI, p=0.346). There was a trend towards double OS in patients who were younger than 72 years of age (26.12 months 3.37-48.87, 95% CI versus 12.75, 0-31.55, 95% CI, p=0.68). Caucasians had greater than 6 times OS than African Americans, and this was statistically significant (26.12 months, 10.42-41.82, 95% CI versus 4.44 months, 0-10.85, 95% CI, p=0.015). Frontline use had a clinically significant difference in OS compared to salvage use (22.67 versus 4.53 months, p=0.200).
The median OS in patients with favorable risk disease was approximately 3 times greater than the adverse risk group (22.67 versus 8.87 months, p=0.449). While not of statistical significance, TP53 mutated AML was associated with approximately one third the median OS than non-mutated TP53 AML (7.95 months, 2.75-13.16, 95% CI versus 26.12 months, 0-52.28, 95% CI, p=0.947). Patients who achieved complete remission (CR) after C1 had greater PFS (median 51.91 versus 8.87 months, p=0.033) and OS than those who did not (52.83 months versus 12.75 months, p=0.063).
Conclusions:
We evaluated the use of VEN and HMA in patients with AML treated in an urban setting. Patients received decreasing number of days of VEN each cycle and had increasing number of days between cycles, suggesting treatment reduction and delays due to complications such as neutropenia and infections, however without compromise to OS.
OS analysis was not statistically significant but was clinically significant at 22.67 months, with younger patients, Caucasians, favorable risk disease and frontline use having greater OS. Achieving CR by the end of C1 translated to a benefit in PFS and OS. The presence of TP53 mutation remains a high-risk feature with detrimental effects on OS.
Future work needs to evaluate the impact of race and regimen variations, including VEN reduction and cycle delays, on CR, PFS and OS.