Real-World Experience of Venetoclax Combination Therapy in Patients with Acute Myeloid Leukemia (AML): A Single-Institution Retrospective Study in a Middle-Income Country

Introduction

Venetoclax (VEN) combined with hypomethylating (HMA) agents or intensive chemotherapy (IC) has demonstrated high remission rates, good disease control, and high allogeneic stem cell transplantation (allo-SCT) rates in patients with acute myeloid leukemia (AML) compared to chemotherapy alone. Real-world data are required to confirm findings from phase 3 studies, particularly efficacy in middle-income countries. We describe the survival and response rates in patients with de novo AML and AML secondary to myeloproliferative neoplasms (MPN), and myelodysplastic syndromes (MDS) treated with VEN in combination with HMA or IC in a real-world setting in Santiago, Chile.

Methods

This is a retrospective study of medically fit and unfit patients with AML who received VEN in combination with HMA or IC as first or second-line therapy between October 2018 and August 2022. We included patients with AML (>20% blasts in bone marrow), MDS with increased blasts, or transformed MPN (>10% blasts in the bone marrow or >5% blasts in peripheral blood). Demographic characteristics, cytogenetic abnormalities, molecular information, and treatment including allo-SCT were recorded and included. The Kaplan Meier Method was used for survival analysis and log-rank test for survival comparisons.

Results

This study included 20 consecutive patients from Clínica Alemana in Santiago, Chile. The average age was 71 (range 22-85). Fourteen patients, 14/20 (70%), were older than 65 years. Eleven patients (55%) were ineligible for IC. Secondary AML affected 9 patients (45%). Nineteen patients (95%) had an intermediate or complex karyotype. Next-Generation Sequencing was available in 11 pts. Intermediate or high-risk mutations (FLT3-ITD, ASXL1, BCOR, RUNX1, SRSF2, STAG2 ,U2AF1,BCR/ABL1) were present in 8/20 (40%) of patients.

Of the 20 patients, 12 (60%) were treated with curative intent and 8 (40%) with palliative intent. VEN was given to all patients at some point during treatment, with 14 (70%) as first-line and 6 (30%) as second-line.

Decitabine or azacytidine with VEN were the most used regimens in first-line (13/20, 65%). FLAG-IDA combined with VEN was the most used second-line regimen (5/9, 55%).

One patient died during induction before bone marrow evaluation on day 30. In 19 evaluable patients, the complete response rate (CR+CRi) with VEN was 57% in first line and 44% in second-line. According to flow cytometry, 60% of patients achieved negative measurable residual disease (<10^-3). Overall, eleven patients (55%) were able to proceed to allo-SCT, with a transplant rate of 11/12 patients (92%) in the curative intention group.

The 2 year Event-Free Survival and Overall Survival for the whole group was 56% and 66% respectively with a statistically significant difference in survival between the curative and palliative intention group (Figure 1).

Conclusions Real-world data from a middle-income country institution confirms that VEN combined either with HMA or IC provides high remission rates and adequate disease control in this elderly group of patients with AML treated with curative intention. VEN is useful as a bridge for transplant and should be incorporated early during induction treatment in patients with AML.

No relevant conflicts of interest to declare.