Abstract
BACKGROUND: Elderly patients with relapsed acute myeloid leukemia (AML) have limited treatment options and a poor prognosis. Venetoclax combined with azacitidine has shown promising activity in newly diagnosed or relapsed/refractory AML, but real-world data on older populations remain scarce. This study aimed to evaluate the efficacy, safety, and prognostic factors - including select blood biomarkers - of venetoclax plus azacitidine in elderly patients with relapsed AML. METHODS: We conducted a single-center retrospective review of patients aged ≥65 years diagnosed with relapsed AML who received venetoclax plus azacitidine between January 2018 and December 2022. Patient demographics, baseline disease characteristics, and treatment details were collected. Blood biomarkers, such as lactate dehydrogenase (LDH), C-reactive protein (CRP), and selected molecular markers (including FLT3-ITD and NPM1 mutations), were also assessed at baseline to evaluate their prognostic value. The primary endpoint was the overall response rate (ORR), defined as the sum of complete Remission (CR) and CR with incomplete hematologic recovery (CRi). Secondary endpoints included overall survival (OS), event-free survival (EFS), and safety. Prognostic factors were identified through univariate and multivariate analyses using Cox proportional hazards models. Survival curves were constructed via the Kaplan-Meier method. RESULTS: A total of 50 patients (median age, 72 years; range, 65-82) met the inclusion criteria. The ORR was 60% (40% CR and 20% CRi). The median OS was 9.2 months (95% CI: 6.8-11.5), and the median EFS was 6.0 months (95% CI: 4.2-8.3). Common Grade 3-4 adverse events included neutropenia (46%) and thrombocytopenia (32%). The 30-day treatment-related mortality rate was 4%. Elevated baseline LDH (≥ the upper limit of normal) was associated with reduced OS (p=0.03). Patients with high CRP levels and/or adverse molecular markers, such as FLT3-ITD positivity, also showed a trend toward poorer survival, which, however, did not reach statistical significance in the multivariate model. Multivariate analysis confirmed poor Eastern Cooperative Oncology Group (ECOG) performance status, baseline LDH level, and adverse cytogenetics as independent predictors of reduced OS. CONCLUSION: Venetoclax combined with azacitidine demonstrated encouraging efficacy and manageable toxicity in this retrospective analysis of elderly patients with relapsed AML. Elevated LDH and adverse molecular/cytogenetic profiles were associated with worse outcomes. These findings highlight the importance of integrating blood biomarker assessment into routine evaluation and suggest venetoclax-based regimens may be a viable therapeutic option in older, relapsed AML populations. Prospective multicenter studies are warranted to confirm these results and refine patient selection.