Patients with newly diagnosed acute myeloid leukemia (AML) who are aged 75 years or older or ineligible for intensive chemotherapy may have improved outcomes with a longer 10-day course of decitabine with venetoclax, according to research published in The Lancet Haematology.

Older patients tend to have poor overall survival at 3 years (10-30%). Patients with relapsed or refractory AML have less than a 10% overall survival at 3 years. Venetoclax with hypomethylating agents, such as decitabine, has become the standard of care for newly diagnosed patients with AML who are aged 75 or older or unfit for intensive chemotherapy.

A standard course of decitabine is 5 days, but a single-center phase 2 trial sought to determine if a longer 10-day course would convey more benefit for high-risk subgroups. The primary endpoint was overall response rate (ORR).

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The trial enrolled 168 patients: 70 with newly diagnosed AML, 15 with untreated secondary AML, 28 with treated secondary AML, and 55 with relapsed or refractory AML. The median age was 71 years.

Patients received 20 mg/m2 of intravenous decitabine for 10 days with oral venetoclax at 400 mg daily for induction. Venetoclax with 10-day decitabine had a manageable safety profile, with good responses. The ORR was 74%; 103 patients experienced complete remission (CR) or complete remission with incomplete hematological response (CRi). Patients with newly diagnosed AML had an ORR of 89%, while patients with relapsed or refractory disease had an ORR of 62%.

Patients who had a CR had higher overall survival (OS) of 22.1 months, compared with patients who had CRi (OS, 8 months) or no response (OS, 3.3 months). Infections with grade 3 or 4 neutropenia and febrile neutropenia were the most common adverse events with the 10-day treatment. The treatment regimen had a low 30-day mortality of 3.6% for all patients.

Overall, the authors concluded that venetoclax with 10-day decitabine has a tolerable safety profile and has high activity in newly diagnosed AML and high-risk subgroups. Study limitations include the single-center design and heterogeneity of the patient population. Future trials are needed to clarify activity in molecular subsets of AML and other high-risk groups.

Disclosures: Some authors have declared affiliations with or received grant support from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.


DiNardo CD, Maiti A, Rausch CR, et al. 10-day decitabine with venetoclax for newly diagnosed intensive chemotherapy ineligible, and relapsed or refractory acute myeloid leukaemia: a single-centre, phase 2 trial. Lancet Haematol. Published online September 4, 2020. doi:10.1016/S2352-3026(20)30210-6