Clinical Utility of Frailty Scoring in Elderly Acute Myeloid Leukemia Patients Treated With Venetoclax and Hypomethylating Agents

Q: How was frailty measured in this study of elderly AML patients?

Frailty was assessed using the Clinical Frailty Scale (CFS). Patients with score ≤ 3 were classified as low frailty, and those with score > 3 were classified as high frailty.

Sep 30, 2026

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Acute myeloid leukemia (AML) in elderly patients creates major treatment barriers because many individuals are considered unfit for intensive chemotherapy due to age, comorbidities, and frailty. In a retrospective single-center analysis of 52 treatment-naïve patients receiving venetoclax plus azacitidine or decitabine, frailty was scored using the Clinical Frailty Scale (CFS). Higher frailty (CFS > 3) predicted worse survival and higher infection rates, while lower frailty and azacitidine-based therapy independently related to improved outcomes. The study supports routine frailty-based stratification to guide individualized venetoclax–HMA treatment and supportive care selection.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages9

Reading Time23 min

AccessFree to download

Introduction

Rationale for frailty assessment in elderly AML

Venetoclax plus hypomethylating agents as standard of care

Persistent limitations in survival with HMA-based therapy

Study focus and objective

European Journal of Haematology ORIGINAL ARTICLE OPEN ACCESS Clinical Utility of Frailty Scoring in Elderly Acute Myeloid Leukemia Patients Treated With Venetoclax and Hypomethylating Agents Ernesto Vigna1 | Antonella Bruzzese1 | Enrica Antonia Martino1 | Andrea Corsonello2,3 | Santino Caserta1 | Caterina Labanca1 | Francesco Mendicino1 | Eugenio Lucia1 | Virginia Olivito1 | Nicola Amodio4 | Fortunato Morabito5 | Massimo Gentile1,3 1Hematology Unit, Department of Onco-Hematology, AO of Cosenza, Cosenza, Italy | 2Unit of Geriatric Medicine, Italian National Research Center on Aging (IRCCS INRCA), Cosenza, Italy | 3Department of Pharmacy, Health and Nutritional Science, University of Calabria, Rende, Italy | 4Department of Experimental and Clinical Medicine, University of Catanzaro, Catanzaro, Italy | 5AIL Sezione di Cosenza, Cosenza, Italy Correspondence: Ernesto Vigna ([ernesto.vigna@aocs.it](ernesto.vigna@aocs.it)) | Massimo Gentile ([massimo.gentile@unical.it](massimo.gentile@unical.it)) Received: 26 August 2025 | Revised: 14 October 2025 | Accepted: 17 October 2025 Funding: The authors received no specific funding for this work. Keywords: AML | frailty | therapy ABSTRACT Acute myeloid leukemia (AML) in elderly patients presents a major therapeutic challenge, as many are deemed unfit for intensive chemotherapy due to age, comorbidities, or frailty. Venetoclax in combination with hypomethylating agents (HMA) has emerged as a standard-of-care for this population, yet outcomes remain heterogeneous and predictive tools are limited. In this retrospective singlecenter study, we analyzed 52 treatment-naïve AML patients receiving venetoclax combined with either azacitidine (n = 33) or decitabine (n = 19) at the Hematology Department of Cosenza Hospital between August 2021 and June 2025. Frailty was assessed using the Clinical Frailty Scale (CSHA CFS), with 19 patients classified as low frailty (score ≤ 3) and 33 as high frailty (score > 3). The median age was 75.3 years (range 58.2–89.2), and the cohort included 33 de novo and 19 secondary AML cases. After a median follow-up of 18 months, 34 patients (65.4%) had died: 14 due to disease progression, 12 due to treatment-related toxicity—predominantly severe infections—and 5 from unrelated causes. ROC curve analysis showed that a CFS score > 3 was associated with worse survival (AUC 0.75, 95% CI 0.61–0.89, p< 0.004), with median overall survival of 7.6 months for low-frailty patients versus 2.5 months for high-frailty patients (1-year OS 44.1% vs. 18.7%, p = 0.031). Multivariate analysis confirmed that lower frailty (p = 0.031) and azacitidine-based therapy (p = 0.025) were independently associated with improved survival. Overall response rate was 48%, including 21 complete responses (CR/CRi) and 4 partial responses. Frailty was the only significant predictor of response (p = 0.005), whereas age, sex, typeof AML, ELN risk score, renal function, BMI, or type of HMA did not significantly influence outcomes. Grade 3–4 treatment-related adverse events occurred in all patients, predominantly hematological; non-hematological events included infections (61.9%), cardiotoxicity (11.9%), and liver toxicity (9.5%). High-frailty patients experienced a higher incidence of infections (72.7% vs. 36.8%, p = 0.02) and hospitalizations (57.6% vs. 21.1%, p = 0.011). These results suggest that the CSHA CFS is a simple and clinically meaningful tool to stratify elderly AML patients for venetoclax–HMA therapy, identifying those at higher risk of treatment-related complications and poor survival. Incorporating frailty assessment into routine practice may enhance patient selection, optimize supportive care, and guide individualized therapeutic decisions. Prospective, multicenter studies are warranted to validate these findings and refine the use of frailty-guided treatment strategies in this vulnerable population. | Ernesto Vigna and Antonella Bruzzese equally contributed as the fir

FAQs

How was frailty measured in this study of elderly AML patients?

Frailty was assessed using the Clinical Frailty Scale (CFS). Patients with score ≤ 3 were classified as low frailty, and those with score > 3 were classified as high frailty.

What relationship did CFS have with survival outcomes?

A CFS score > 3 was associated with worse survival, with lower frailty patients showing a median overall survival of 7.6 months versus 2.5 months in high-frailty patients.

Which factors were independently associated with improved survival?

Multivariate analysis confirmed that lower frailty (p = 0.031) and azacitidine-based therapy (p = 0.025) were independently associated with improved survival.

Sep 30, 2026

Uploaded by Ezra