Real-World Treatment Patterns and Clinical Outcomes in Newly Diagnosed Acute Myeloid Leukemia with and without mIDH1 Treated with Intensive Chemotherapy from an International Real-World Database (REAL-IDH)

Introduction

Intensive chemotherapy (IC) remains the main backbone therapy in fit, newly diagnosed, acute myeloid leukemia (AML) patients. Clinical trials assessing the efficacy of IC under-represent select subgroups of patients, such as those with certain comorbidities, unique characteristics, or rare genomic abnormalities. Real-world data provides additional insights into treatment patterns and clinical outcomes in patients with AML receiving first-line IC. REAL-IDH is an international network that generates evidence to improve real-world understanding of AML, including patients with a mutation in the gene encoding isocitrate dehydrogenase 1 (m IDH1). This abstract presents data from the REAL-IDH study, specifically on treatment patterns and outcomes in newly diagnosed AML patients who were treated with IC, including those with or without m IDH1 disease.

Methods

This retrospective, longitudinal, observational study was conducted using databases from the USA (Cancer Outcomes Tracking and Analysis [COTA]), UK (Cancer Analysis System [CAS]), and France (DATAML registry). Data were collected on adult patients with newly diagnosed AML between 2013-2020 (USA and UK) and 2017-2021 (France).Similar inclusion/exclusion criteria were applied across countries. Here we report treatment patterns, efficacy and safety outcomes, including complete (CR) and partial response (PR), CR with incomplete count recovery (CRi), minimal residual disease (MRD), morphological leukemia-free state (MLFS), time to treatment response (TTR), objective response rate (ORR; defined as rate of CR, CRi, PR and MLFS in the total treated population), mortality rate, and overall survival (OS) in patients receiving first-line IC.

Results

13,013 patients with AML were included in the REAL-IDH study, with 7406 eligible patients receiving IC as first-line treatment (USA: n=1145; France: n=800; UK: n=5461). In the IC population, of those tested for the IDH mutation, m IDH1 was detected in 70 (6.1%), 84 (10.5%), and 15 (9.3%) patients in the USA, France, and UK, respectively.

The most frequent first-line IC, in all three databases, was cytarabine + anthracycline (7+3 regimen) in the total populations and in the m IDH1 and wild-type subgroups. In France, lomustine was added to 7+3 in patients >60 years. The most frequent second-line therapy in the whole IC population was salvage chemotherapy with high-dose or intermediate-dose cytarabine or a combination of either of these with anthracycline (daunorubicin, idarubicin, or amsacrine) in France and decitabine or the combination of cytarabine, etoposide and mitoxantrone in the USA. Azacitidine/venetoclax combination was used in second and third line in France and USA and it was the most frequent third-line therapy (35.8%) in France. Patients received IC in combination with targeted therapies (mainly midostaurin) in 18% of the IC population in France and 12.4% of the IC population in the USA.

Rates of CR, MLFS, TTR and ORR were similar in the USA and France ( Table 1). Mortality rates were similar across all three countries ( Table 1).

Adverse events (AE) were reported in 43.7% of patients (500; N=1145) in the USA and 76.3% (610; N=800) in France with a reported infection in 13% (149; N=1145; CTCAE coded infection AE) and 43.1% (345; N=800; fungal/bacterial at induction or during treatment; septic shock/pneumopathy at induction or during first 3 months of treatment leading to admission to an intensive care unit; or infection leading to death) of patients in the USA and France, respectively.

Conclusion

This large-scale population-based study provides insight into treatment patterns and clinical outcomes in patients with AML who received first-line IC in the real-world setting, including patients with or without m IDH1 disease. Intensive treatment combinations have not significantly changed over the past decade with the exception of the addition of targeted therapies. Despite the lack of a common standard IC regimen and protocol across countries, and different healthcare systems, mortality rates were similar with IC across each country. In the REAL-IDH study we observed that treatment patterns in m IDH1 or wild type patients were similar. More specific data is needed regarding the sequencing of treatment regimens and overall outcomes in m IDH1 AML patients.