Uptake of Novel Therapies into First-Line Treatment for AML Patients - EU5 Perspective

Introduction: Treatment options for acute myeloid leukaemia (AML) patients have increased in recent years as several novel targeted medications for AML patients have been introduced. The aim of this study was to identify the integration of novel treatment concepts in the standard of care for AML patients, using real-world treatment information and to investigate evidence for therapeutic benefits of novel agents in this population.

Methods: 255 haemato-oncologists in EU5 countries participated in a retrospective longitudinal reporting of patients with AML, who started therapy between January 2018 and March 2020. Data recorded for each patient included cytogenetic and European LeukemiaNet (ELN) prognostic factors, medical history, treatment pathway starting with first-line therapy, response and survival data.

Results: Data of 1,015 AML patients were available and 967 were considered sufficient in data quality to analyse for the goal of this analysis. The age distribution was balanced below and above the age of 65 years (506 patients < 65 years and 461 elderly patients, i.e., ≥ 65 years of age). Most of the population, i.e., 706 patients (73%, [95% CI 70%-76%]) received intensified therapies based on anthracycline/cytarabine regimen that are considered standard of care. Gemtuzumab ozogamicin was added to intensive chemotherapy backbone for 17 patients (2.4%, [95% CI 1.3%-3.5%]). 416 patients treated with intensive chemotherapy were identified as having FLT3-mutated AML. 34 patients (8.1%, [95% CI 5.5%-10.8%]) from the FLT3-mutated group were treated with midostaurin combined with intensive chemotherapy.

Overall, 261 patients (27% [95% CI 24%-30%] of all analysed patients) were treated with lower intensity regimens, i.e., azacitidine, decitabine, and low-dose cytarabine, with or without combination with venetoclax. Most of the patients in the low-intensity therapy group were in the elderly population (253 patients, 97%, [95% CI 95%-99%]).

Venetoclax was combined with low-intensity therapies in 75 patients (29%, [95% CI 23%-34%]). In an exploratory analysis, venetoclax combined with low-intensity chemotherapy demonstrates a trend for improving the complete response rate in comparison to chemotherapy-only patients.

Conclusions: In EU5, less than 50% of AML patients are treated with novel agents combined with chemotherapy backbone. Following FDA approval of venetoclax for AML, usage of venetoclax-containing low-intensity regimens has been observed in EU5. Although approved for targeted AML patient populations (i.e. CD33-mutated, FLT3-mutated patients), only approximately 10% of appropriate patients are receiving gemtuzumab ozogamicin and midostaurin in the first-line setting.