Long-Term Follow-Up of Elderly Patients with Acute Myeloid Leukemia Treated with Decitabine: A Real-World Study of the Apulian Hematological Network

Abstract

Decitabine, a DNA hypomethylating agent, was approved for use in adults with acute myeloid leukemia (AML) not eligible for standard chemotherapy and is now widely accepted as standard treatment. Although a number of clinical trials demonstrated its benefits in elderly AML patients, older adults and patients with frequent comorbidities are typically under-represented in such settings. Thus, the aim of the present study is to evaluate, in a real-world setting, the effectiveness and toxicity of decitabine administered as a single agent in unselected previously untreated elderly AML patients not eligible for intensive chemotherapy. In nine hematological departments of the Apulian Hematological Network (REP), we enrolled 199 patients (median age: 75.4 years; range: 61–91) with de novo (n = 94) or secondary/therapy-related (n = 105) AML treated with decitabine 20 mg/m2 for five days every 4 weeks. Hazard ratios (HR) and their 95% confidence intervals (CI) were estimated using multivariate Cox regression. The average number of cycles administered per patient was 6.3 (SD: 6.0; median: 5 cycles). Complete response was achieved by 31 patients (15.6%) and partial response by 57 (28.6%), for a total of 88 responders overall (44.2%). After a median follow-up of 33.6 months, median OS was 8.7 months (95% CI: 7.4–10.3), and the 6-month, 1-year, and 3-year OS rates were 62.7%, 37.0%, and 7.1%, respectively. Mortality was increased in AML patients with ≥3 comorbidities (HR = 2.45; 95% CI: 1.18–5.08) vs. no comorbidities and in those with adverse karyotype (HR = 1.58; 95% CI: 1.05–2.38) vs. favourable or intermediate profile. Infection was the main registered adverse event (46.0%). In conclusion, this REP real-life study demonstrates, after a follow-up of almost 3 years, how decitabine administered to AML patients not suitable for intensive chemotherapy is effective and well tolerated, even in a population of truly elderly patients with frequent comorbidities.

Assessment of Measurable Residual Disease on Day 28 of First Induction Chemotherapy in Acute Myeloid Leukaemia Patients

“…A study conducted by Dargenio et al in 2022 found that 6.0% of patients with de novo AML were classified as adverse based on their molecular biology and karyotype profiles. 12 Another study by Buccisano et cytometry was detected in 36.3% of patients. 15 In our study, MRD was slightly higher than some previous international studies.…”

Low-dose decitabine for previously untreated acute myeloid leukemia ineligible for intensive chemotherapy aged 65 years or older: a prospective study based on comprehensive geriatric assessment

“…HMAs are potentially active therapeutic alternatives with improved tolerability compared to intensive chemotherapy for AML. 15 , 36 , 37 Decitabine achieved a response rate of 26% in a multicenter trial in older patients with AML who were unfit for standard chemotherapy. 15 , 38 Currently, no optimal decitabine-dosing regimen is recommended.…”

The Role of Venetoclax in Relapsed/Refractory Acute Myeloid Leukemia: Past, Present, and Future Directions

“…Driven by the promising efficacy data on heavily pretreated patients and the relatively favorable toxicity profile, the clinical development of VEN in AML rapidly shifted towards the frontline setting for elderly/unfit patients, where therapeutic standards [20][21][22] (HMAs and low-dose cytarabine (LDAC)) had been providing unsatisfactory outcomes in clinical practice [23][24][25][26][27]. Moreover, the possibility of increasing treatment efficacy without excessive toxicity with an orally available drug was valuable.…”