VENETOCLAX-BASED AML regimen improves remission and survival outcomes in older or unfit patients with newly diagnosed acute myeloid leukaemia, according to findings from a Phase II study evaluating alternating low intensity treatment combinations.
High Remission Rates with Venetoclax-Based AML Regimen
The study assessed cladribine plus low dose cytarabine and venetoclax alternating with azacitidine plus venetoclax in 190 patients with newly diagnosed acute myeloid leukaemia. The median patient age was 68 years, with ages ranging from 47–84 years, and 13% of patients were aged 75 years or older. According to the European LeukemiaNet 2022 classification, 16% of patients were categorised as favourable risk, 20% as intermediate risk, and 64% as adverse risk.
Investigators reported complete remission or complete remission with incomplete blood count recovery rates of 84% overall. Minimal residual disease negative complete remission or complete remission with incomplete blood count recovery was achieved in 75% of patients.
Among patients with TP53 wild type acute myeloid leukaemia, remission outcomes were higher, with complete remission or complete remission with incomplete blood count recovery observed in 91% of patients and minimal residual disease negative responses achieved in 77%.
Survival Outcomes in Older Patients with Acute Myeloid Leukaemia
The venetoclax-based AML regimen was associated with encouraging long-term outcomes. Median overall survival reached 52 months, while median event free survival was 50 months. The 2 year and 5-year overall survival rates were 60% and 45%, respectively. Event free survival rates at 2 years and 5 years were 56% and 43%, respectively.
Patients achieving minimal residual disease negative complete remission demonstrated particularly durable outcomes. Median overall survival was not reached in this group, and the 2-year overall survival rate was 70%.
Among patients who responded to treatment, 44% proceeded to allogeneic haematopoietic stem cell transplantation, highlighting the regimen’s potential to support transition to curative intent strategies in selected individuals.
Safety Profile and Recovery Outcomes
Early mortality rates remained low throughout the study. Mortality at 4 weeks was 1%, increasing to 3% at 8 weeks. Investigators also reported manageable haematologic recovery times following induction therapy. Median time to absolute neutrophil count recovery above 1×109/L was 27 days, while platelet recovery above 100×109/L occurred after a median of 24 days.
The treatment was considered safe overall, with most Grade 3 and Grade 4 adverse events related to infectious complications. Researchers concluded that the venetoclax-based AML regimen generated high remission rates that translated into favourable long-term outcomes for older or unfit patients with newly diagnosed acute myeloid leukaemia.
Reference
Kadia TM et al. Cladribine with low-dose cytarabine and venetoclax alternating with azacitidine and venetoclax for newly diagnosed acute myeloid leukemia. Am J Hematol. 2026; https://doi.org/10.1002/ajh.70328.
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