Cardiovascular Risk Factors Limit Anthracycline Use in Non-Hodgkin Lymphoma

Non-Hodgkin lymphoma (NHL) patients who have preexisting cardiovascular risk factors are at an increased risk of heart failure, according to a large population-based study. 

“Much of our understanding of heart failure risk in NHL survivors arises from clinical trials that exclude patients with comorbidities, clinical populations that are not necessarily representative of larger populations, or cohorts of childhood cancer survivors who do not have cardiovascular risk factors before their cancer diagnosis,” wrote study authors led by Talya Salz, PhD, of Memorial Sloan Kettering Cancer Center in New York. Anthracycline use can raise the risk of heart failure, but the role of patients’ preexisting cardiovascular risk is not well understood.

This study included 2,508 survivors of NHL included in Danish registries, as well as 7,399 sex- and age-matched healthy controls. Patients had a median age at diagnosis of 62 years, and were followed for a median of 2.5 years. Results of the analysis were published in the Journal of Clinical Oncology.

In the cohort of NHL survivors, 92% were treated with an anthracycline-containing regimen. Thirty-nine percent of survivors had preexisting cardiovascular risk factors, including hypertension, dyslipidemia, and diabetes; 31% had one such factor and 8% had two or more. Among the general population controls, these rates were 29% and 7%, respectively. Eleven percent of the survivors had a history of vascular disease, and 2% had a history of intrinsic heart disease; the rates were the same in the general population cohort.

Compared with the control patients, the NHL survivors had a hazard ratio (HR) for heart failure of 1.42 (95% CI, 1.07–1.88). On a multivariate analysis, the number of cardiovascular risk factors in the survivors was associated with increased risk: one vs zero factors had an HR of 1.63 (95% CI, 1.07–2.47), and two vs zero had an HR of 2.86 (95% CI, 1.56–5.23; joint P < .01).

Preexisting intrinsic heart disease was also associated with an increased risk of heart failure, with an HR of 2.71 (95% CI, 1.15–6.36), but vascular disease was not. The authors noted that there was evidence of confounding by indication. The prescription of anthracyclines was significantly associated with the number of cardiovascular conditions and preexisting heart disease-NHL patients with these risk factors were prescribed anthracyclines less frequently.

“This confirms common practice among oncologists for limiting the use and dosage of anthracyclines in older patients with multiple cardiovascular risk factors,” the authors wrote. “The balance of potential benefits and harms in the use of anthracyclines as part of curative therapy for aggressive NHL should be considered with upfront therapy.”