Low-Dose Decitabine Plus Venetoclax As Frontline Treatment of Acute Myeloid Leukemia

Purpose Hypomethylating agents (HMAs) (5-azacytidine or decitabine) in combination with venetoclax is standard of care in the management of elderly patients with acute myeloid leukemia (AML) ineligible for intensive chemotherapy. Nevertheless, treatment toxicity, in particular bone marrow suppression remains a challenging treatment-related aspect in the care of these patients. Lower than standard dose of decitabine (low-dose decitabine) exerts its effect via induction of cellular differentiation by epigenetic regulation, thus avoiding generalized cytotoxic effects. We assessed the clinical efficacy and patient tolerability of low-dose decitabine (LDDec) in elderly de novo AML patients. Patients and Methods This is a prospective single-center analysis of patients diagnosed with acute myeloid leukemia treated with twice weekly low-dose decitabine (0.2 mg/kg) as first-line treatment. In case of relapsed/refractory disease, standard venetoclax (VEN) was added. Results From the patient cohort comprising 8 patients, the overall response rate [(complete remission (CR) + complete remission with incomplete hematologic recovery (CRi), partial remission (PR)] was 50% (N = 4) with single agent LDDec. The median overall survival was 6.5 months, with 2 patients exceeding 1 year of survival. Next-generation sequencing (NGS) panel study of three patients suggested an effective reduction of SF3B1 mutant clones treated with LDDec/VEN, while SRSF2 mutant clones responded to single agent LDDec. Conclusion Treatment regimens based on low-dose decitabine might be a suitable, less toxic, and clinically effective alternative for elderly patients with de novo acute myeloid leukemia unable to tolerate intensive chemotherapy and possibly at risk of significant myelotoxicity associated with venetoclax combination therapy.