AML Trial Halted Due to COVID-19 Pandemic
March 30, 2020 09:08pm
By Lisa Astor
Researchers have developed a baseline score to determine the risk for heart failure in patients with acute leukemias, to address the scarcity in knowledge around the increasing incidence and risk factors of symptomatic heart failure in this patient population. The findings were published in JACC: CardioOncology.
Marielle Scherrer-Crosbie, MD, PhD
Researchers have developed a baseline score to determine the risk for heart failure in patients with acute leukemias to address the scarcity in knowledge around the increasing incidence and risk factors of symptomatic heart failure in this patient population. The findings were published inJACC: CardioOncology.1
“While we are more effective at treating cancer, the improved survival rates have helped to unmask the cardiotoxic impact of some of the most common cancer therapies,” Marielle Scherrer-Crosbie, MD, PhD, a co-author of the study and a professor of cardiovascular medicine in the Perelman School of Medicine at the University of Pennsylvania, said in a press statement.2“Our hope, in creating this risk score system, is to help clinicians identify patients with the highest risk for potential cardiac damage, so they can more closely monitor the patients via a multidisciplinary approach.”
The study enrolled 645 patients with acute myeloid leukemia (AML) and acute lymphocytic leukemia (ALL). About 450 of those patients were included in the study cohort and followed for a median of 16 months (range, 1-32 months). Symptomatic heart failure developed in 8.9% of the patients (n = 40), which included 1 patient with decompensated heart failure who then died. The median time to development of heart failure was 10 months (range, 1-76). Death due to a noncardiac cause occurred in 47.8% of patients (n = 215).1
At baseline, most patients (included and excluded) had similar characteristics. Of the patients who were enrolled in the study, 67% had AML (n = 301) and 33% had ALL (n = 149). Forty-eight percent of patients were male and had an average age of 51 years (± 15). The most common baseline cardiovascular disease characteristics were current/previous smoking (40%), having ≥2 cardiovascular risk factors (39%), hypertension (36%), and hypercholesterolemia (22%). Yang et al found that those patients who developed heart failure development were typically older, had previous heart failure, had atrial fibrillation, and had pre-existing cardiovascular diseases.
Baseline echocardiographic findings showed that patients with heart failure had a wider index of left ventricular end-diastolic and -systolic volumes with lower left ventricular ejection fraction (LVEF) versus patients with noncardiac death and those who did not experience heart failure events. Global longitudinal strain (GLS) values appeared to be poorer in patients who had heart failure at baseline than in patients with noncardiac death and those with no events.
Intraclass correlation coefficients (ICCs) were measured to determine the reliability of LVEF and GLS. For intraobserver variability, the ICC was 0.92 for LVEF and 0.91 for GLS. For, interobserver variability, the ICC was 0.88 for LVEF and 0.89 for GLS.
The risk score (0 to 21 points) was developed after an analysis of key variables. From the analysis, the investigators determined that age ≥60 years, presence of pre-existing cardiovascular disease, presence of AML, baseline LVEF <50%, and baseline GLS >15% were the appropriate variables for determining the risk score. Patients were then divided into low (score of 0 to 6), medium (score of 7 to 13), and high (score of 14 to 21) risk groups.
The risk of heart failure and noncardiac mortality was found to be higher in patients with AML (52.8% and 34.9%) than in those with ALL (11.6% and 3.4%;P<.001). Contributing factors to this finding included greater doses of anthracyclines in patients with AML and that patients in the AML group tended to be older. When investigators altered the doses of anthracyclines in patients with AML, symptomatic heart failure was still present (HR, 2.77; 95% CI, 1.01-7.63; P= .048).
A modified risk score was evaluated in patients with ALL. Investigators estimated the cumulative risk of the incidence of heart failure in patients with ALL of low, moderate, and high risk at 1 year and came up with greater than 0.1%, 3.6%, and 17.0% in the respective groups (P<.001).
An exploratory analysis was conducted to show the relationship between risk score, GLS, and overall mortality. It was discovered that the risk score was associated with all-cause death (HR, 1.36; 95% CI, 1.23-1.50;P<.001). Patients in low-risk to moderate-risk groups had a greater survival time than high-risk patients (P<.001). Adjustments were made based on age and leukemia types, but only GLS >15% was found to be independently related to all-cause death (HR, 1.73; 95% CI, 1.30-2.31; P<.001). Baseline LVEF <50% and pre-existing cardiovascular disease were not found to be independently related to overall mortality.