Finite-Duration Venetoclax/Azacitidine Followed by Umbilical Cord Blood Infusion Improves Outcomes in Frail Elderly Patients With Untreated Acute Myeloid Leukemia-A Pilot Study.

BACKGROUND

Continuous venetoclax-azacitidine (VA) therapy is currently the major intervention for elderly or unfit acute myeloid leukemia (AML) patients. However, moderate chemotherapy with finite-duration VA could achieve comparable or superior efficacy to infinite-duration VA. Additionally, umbilical cord blood (UCB) transfusion improves clinical safety for elderly patients. Therefore, this single-center study presents an improved approach: A finite-duration VA and decitabine priming with intermediate-dose cytarabine followed by UCB infusion.

METHODS

We included elderly AML patients who underwent the treatment between March 2021 and May 2024. Induction and maintenance regimens were VA. Our consolidation therapy involved intravenous decitabine (20 mg/m2 d1-3), intermediate-dose cytarabine (1.0 g/m2 q12h d4-5), with subsequent UCB infusion (1.5% ± 25% × 107/kg) d7. Our endpoints included duration of response (DOR), overall survival (OS), and safety.

RESULTS

We analyzed 16 patients with a median follow-up of 53.6 months (95% CI: 36.2-71.0 months), and 7 out of 16 participants were at adverse risk. The median VA cycle number prior to disease relapse was 5 (IQR: 4-6). The median DOR was 17.4 months (95% CI: 7.3-27.5 months), with a 1-year DOR rate of 68.8% and a 2-year DOR rate of 35.2%. The median OS was 24.9 months (95% CI: 9.8-40.1 months), with a 1- and 2-year OS rate of 100% and 55.6%. Specifically, among the 8 patients with IDH1/2 mutations, 4 experienced sustained remission, with 1-year OS of 100%. Hematological and non-hematological toxicities remained manageable during the consolidation phase.

CONCLUSIONS

We demonstrated prolonged survival, particularly in patients with IDH mutations, using the modified intervention. This approach holds significant value for elderly patients with untreated AML who are unfit for standard treatments.