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).

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.


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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.

Reference

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

This article originally appeared on Hematology Advisor