# Addition of Venetoclax to Azacitidine Did Not Improve Survival in Acute Myeloid Leukemia and Was Not Well Tolerated: Real World Experience

## TL;DR

Adding Venetoclax to Azacitidine in AML patients did not improve survival and caused more side effects in real-world treatment.

## Contribution

Real-world evidence showing that combining Venetoclax with Azacitidine does not improve outcomes in elderly AML patients.

## Key findings

- AZA + Ven had higher toxicity with more treatment delays and severe hematological adverse events.
- No significant difference in response rate or overall survival between AZA and AZA + Ven groups.
- Lower tolerability of Venetoclax limited its effectiveness in the real-world setting.

## Abstract

We compared the safety and efficacy of front-line therapy with azacytidine (AZA) alone or in combination with venetoclax (AZA + Ven) in AML patients who were not eligible for induction chemotherapy. AZA was well-tolerated, while only 52% received Ven doses above 200 mg. More patients on AZA + Ven had treatment delays. Hematological adverse events were more common in AZA + Ven groups. There were no differences in response rate and overall survival between AZA and AZA + Ven cohorts. We concluded that in the real-world setting, the addition of Venetoclax to AZA did not improve overall survival or disease control, mainly due to low tolerability and higher toxicity.

Introduction: Front-line therapy with Azacitidine (AZA) + Venetoclax (Ven) improved overall survival (OS) and remissions in acute myeloid leukemia (AML) patients ineligible for standard induction. Less is known about the outcome of AML treated with AZA + Ven in the “real world”. Methods: We assessed the comparative pattern of administration, tolerability, efficacy and safety of AZA vs. AZA + Ven administered at our cancer centre. We retrospectively reviewed all patients treated with AZA alone or AZA + Ven. Patients who received less than one cycle or proceeded with consolidative stem cell transplant were excluded. Results: A total of 53 patients, median age 77 years, received AZA, and 23 patients, median age 73 years, received AZA + Ven. Among those, 69% and 47.8% were ≥75 years old, respectively. Only 52% received Ven doses above 200 mg. Mean time on therapy was 13.1 months in AZA vs. 5.9 months in AZA + Ven. Treatment delays occurred in 22.6% of AZA and 34.8% of AZA + Ven patients, primarily due to infections and cytopenias. Neutropenia grade 3/4 occurred in 28.3% of AZA vs. 56.5% of AZA + Ven patients. Thrombocytopenia grade 3/4 occurred in 15.1% of AZA and 51.2% of AZA + Ven patients. Anemia grade 3/4 occurred in 5.7% of AZA vs. 30.4% of AZA + Ven patients. Moreover, 69.8% of AZA and 69.5% AZA + Ven patients reached stable disease/partial and complete remission. Median overall survival (OS) was similar: 18 months in AZA vs. 14 months in the AZA + Ven group, p = 0.905. Conclusions: In a community setting, the addition of Venetoclax to AZA did not improve overall survival or disease control, mainly due to low tolerability and higher toxicity. However, these results should be interpreted cautiously due to a significant imbalance in the cytogenetic risk profiles and lower tolerability in the combined group. This suggests the need for a larger study with adjusted analyses.