SOHO 2026 Annual Meeting

Weekly Metronomic HMA + Venetoclax in Older Adults with Myeloid Neoplasms: A Real-World Experience

Mahmood Aldapt, MD¹; Talha Badar, MD¹; Antoine N. Saliba, MD²; Sidney Bianco, NP¹; Catherine Hanratty, NP¹; James Foran, MD¹; Hemant Murthy, MD¹

¹ Division of Hematology and Medical Oncology, Mayo Clinic, Jacksonville, FL, USA

² Division of Hematology and Medical Oncology, Mayo Clinic, Rochester, MN, USA

INTRODUCTION

•HMA + venetoclax (VEN) is standard of care for older or unfit AML: VIALE-A reported cCR ~66% and median OS 14.7 months.¹

•Standard 28-day VEN causes prolonged myelosuppression and heavy transfusion needs — limiting use in frail, comorbid, or transfusion-restricted patients.¹

•Metronomic weekly dosing + all-oral decitabine-cedazuridine (DEC-C) enables flexible, outpatient, low-intensity delivery.², ³

AIM

•To describe real-world clinical outcomes with weekly metronomic HMA + VEN in an older, heavily comorbid myeloid-neoplasm cohort at a single center.

•Outcomes assessed included response rate, overall survival, event-free survival, treatment duration, transfusion independence, and grade 3–4 therapy-related cytopenias.

METHOD

•Design: Retrospective single-center review (Mayo Clinic, Jacksonville, FL)

•Cohort: 19 patients, 16 AML, 2 MDS-IB, 1 CMML, treated July 2024 to October 2025

•Regimen: Weekly HMA + VEN; VEN dose adjusted for CYP3A4 inhibitors

•Response: ELN 2022 AML criteria⁴

•Risk: ELN 2024 for less-intensive therapies⁵

RESULTS

•Cohort. Nineteen patients (16 AML, 4 de novo, 12 sAML/MRC/tAML; 2 MDS-IB1/2; 1 CMML) were treated between July 2024 and October 2025. Median age was 79 years (range 68–90), with a median of 2 comorbidities (range 0–7). ECOG PS was 0–1 in 66.7% and 2–3 in 33.3%.

•Regimen. Weekly HMA + VEN was delivered as induction in 8 patients (42.1%) and as maintenance after standard-dose HMA/VEN in 11 (57.9%). Seventeen patients (89.5%) received all-oral decitabine/cedazuridine 35/100 mg + VEN weekly; 1 received subcutaneous decitabine 0.2 mg/kg + VEN; 1 received IV decitabine 20 mg/m² + VEN.

Response and survival. Median treatment duration was 21.6 weeks (range 1–64). Median time to response was 2.9 months. Median overall survival was 11.7 months (median follow-up 9.3 months); median event-free survival was 10.4 months. Seven deaths occurred, all disease-related

CONCLUSIONS

•Weekly metronomic HMA + VEN, delivered predominantly as an all-oral regimen — was clinically active in an older, heavily pretreated, high-comorbidity population.

•Attenuated myelosuppression and outpatient convenience make this approach applicable in frail patients and transfusion-restricted populations.

SOHO 2026 Annual Meeting

Weekly Hypomethylating Agent and Venetoclax Combination Therapy in Myeloid Neoplasms: A Real-World Single-Center Experience in an Older, High-Comorbidity Population

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