INTRODUCTION

Venetoclax combined with hypomethylating agents (VEN/HMA) is the standard of care for older/unfit patients with AML, yet patients with severe renal impairment were excluded from the pivotal VIALE-A trial.

AIMS

Pharmacokinetic data suggest no dose adjustment is required for CrCl ≥15 mL/min, but clinical outcomes data in this population remain limited to small retrospective series. We aimed to evaluate the safety and efficacy of VEN/HMA in AML patients with pre-existing severe CKD.

METHODS

➢ Using the TriNetX Global Network, we identified adults with newly diagnosed AML who received venetoclax with azacitidine or decitabine (initiated within 14 days).

➢ Two cohorts were defined: Severe CKD (CKD stage 3b, 4, 5, ESRD diagnosed on or before AML diagnosis; n=302) and No Severe CKD (absence of these diagnoses; n=6,291).

➢ 1:1 propensity score matching (PSM) was performed for demographics (age, sex, race, ethnicity),

comorbidities (HTN, IHD, CVA, HF, COPD, DM), baseline laboratory values (leukocytes, platelets,

erythrocytes, LDH), and prior HMA exposure.

➢ Outcomes included 1-year overall survival (OS); 90-day tumor lysis syndrome (TLS), acute kidney injury (AKI), and sepsis; and 1-year remission and relapse rates; calculated from first VEN/HMA administration.

RESULTS

• ➢  One year mortality was significantly higher in the severe CKD cohort (57.9% vs. 46.3%; RR 1.25, 95% CI 1.07–1.46; OR 1.60, 95% CI 1.15–2.21; p=0.005).

• ➢  Ninety-day TLS incidence was significantly elevated (16.4% vs. 9.1%; RR 1.82, 95% CI 1.17–2.82; OR 1.98, 95% CI 1.20–3.26; p=0.007).

• ➢  Ninety-day AKI was markedly more frequent (45.6% vs. 27.9%; RR 1.64, 95% CI 1.31–2.04; OR 2.18, 95% CI 1.55–3.06; p0.001).

• ➢  Ninety-day sepsis rates were comparable (25.8% vs. 24.2%; p=0.45).

• ➢  One-year remission trended lower insignificantly in the CKD cohort (31.4% vs. 38.6%; OR 0.73, 95% CI 0.51–1.05; p=0.085)

• ➢  1-year relapse wasn’t significantly different (22.8% vs. 22.9%; p=0.99).