Oral decitabine/cedazuridine + venetoclax in ND AML: Phase II long-term follow-up

Results from the long-term follow-up of a single-center, phase II study (NCT04746235) evaluating oral decitabine/cedazuridine + venetoclax in patients with newly diagnosed (ND) acute myeloid leukemia (AML) who were older or considered ineligible for intensive chemotherapy (IC; N = 68) were published in Haematologica by Htut et al. The primary endpoint was overall response rate (ORR), defined as patients achieving complete remission (CR), CR with incomplete hematologic recovery (CRi), partial remission (PR), or morphologic leukemia-free state (MLFS). 

Key data: The ORR was 75% in patients with de novo AML (n = 32) and 58% in those with secondary AML (n = 36); among responders, measurable residual disease (MRD) negativity was achieved in 58% and 56% of patients, respectively. At a median follow-up of 32 months, median overall survival (OS) was 12.7 months (95% confidence interval [CI], 9.1–20.3) in patients with de novo AML vs 7.2 months (95% CI, 3.6–29.9) in those with secondary AML (p = 0.61). Among patients achieving CR or CRi, median relapse-free survival (RFS) was 9.2 vs 11.7 months in patients with de novo vs secondary AML (p = 0.56). Grade ≥3 treatment-emergent adverse events (TEAEs) occurred in 65% of patients; the most common were thrombocytopenia (15%) and febrile neutropenia (12%).

Key learning: Oral decitabine/cedazuridine + venetoclax demonstrated encouraging response rates in patients with ND AML who are older or ineligible for IC, with a higher ORR in patients with de novo vs with secondary AML. However, there was no statistically significant difference between survival outcomes in patients with de novo vs secondary AML. These data highlight the need for improved therapeutic approaches for patients with secondary AML.