From Cytotoxic to Senolytic: Decitabine and Venetoclox as the New 7+3 for AML Induction, Crossing the Barrier of Frailty

Abstract

Background: nowadays Hypomethylating arm (HMA) with venetoclax (VEN) arm, became standard for care patients with acute myeloid leukemia (AML). The venetoclax was recommends as continuous 28-day cycles, but shortened VEN durations may induce similar response rates and improve tolerability.

Methods:  We performed a descriptive prospective, single center study. Twenty one AML patients (both unfit and fit patient), were enrolled in non-randomized trial, for chemotherapy of venetoclax with decitabine (DEC3-VEN) regimen, by (DEC; 20 mg/m2; IV days 1-3) Patients admitted for 7 days oral venetoclax 200mg daily for induction).

Results: Between January and December, 2024, we enrolled 21 Adults newly confirmed AML patients. The median age was 53 years (26–80) and 62% patients had ECOG performance state of 2 or higher. Endpoints of the trial included response rates evaluated as remission rate as (complete remission [CR]in 52% of patients, CR with incomplete blood count recovery [CRi] in 10%, partial remission (PR) 14% while not response (NR) in 24%. The best age for CR was forties and the worst non responded age was (60 yrs). The noted toxicity effects appeared as neutropenia (90.5%), anemia (38.1%), thrombocytopenia (33.3%), and typhlitis (19%) pericarditis, splenic infraction, skin rash and sepsis represent (4.8%) for each. Also the responders had the lowest HB, white blood cell, platelets, and myeloid blasts counts, than non-responders.

Conclusions: the venetoclax combined with short three sessions of DEC (DEC3-VEN) is so effective and relatively safe induction therapy regimen for AML patients from different age. Nevertheless, the relatively limited survival benefits and response rates necessitate the need for further digging in this field.