Cumulative anthracycline exposure and risk of cardiotoxicity; a Danish nationwide cohort study of 2440 lymphoma patients treated with or without anthracyclines

Abstract

Summary Cardiotoxicity is a known risk of anthracycline treatment. However, the relative contribution of anthracyclines to the development of congestive heart failure (CHF), when included in a poly‐chemotherapy regimen, is unclear. We examined cardiotoxicity in adult patients with diffuse large B‐cell lymphoma and follicular lymphoma undergoing first‐line immunochemotherapy from 2000–2012. In total, 2440 patients without previous heart disease were identified from the Danish Lymphoma Registry, of which 1994 (81·7%) were treated with anthracycline‐containing chemotherapy [R‐CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone) or R‐CHOEP (R‐CHOP + etoposide)] and 446 (18·3%) were treated without anthracyclines (reference group). Compared to the reference group, the adjusted hazard ratio of CHF after 3–5 cycles of R‐CHOP/CHOEP was 5·0 [95% confidence interval (CI) 1·4; 18·5], 6 cycles 6·8 (95% CI 2·0; 23·3) and >6 cycles 13·4 (95% CI 4·0; 45·0). The cumulative 5‐year risk of CHF with all‐cause mortality as competing risk was 4·6% after 3–5 cycles of R‐CHOP/CHOEP, 4·5% after 6 and 7·9% after more than 6 cycles. Cumulative 5‐year risk for patients treated without anthracyclines was 0·8%. Using anthracyclines in first‐line lymphoma treatment increases risk of CHF in patients without previous history of heart disease. In particular, treatment with >6 cycles of R‐CHOP/CHOEP is associated with a significant increase in CHF rate.

Nonpeghylated liposomal doxorubicin combination regimen (R‐COMP) for the treatment of lymphoma patients with advanced age or cardiac comorbidity

“…Heart failure induced by anthracyclines is unfortunately unpredictable, but it is well‐known that the accumulation of the drug induces a left ventricular dysfunction particularly over a cumulative dose of 450 mg. Other risk factors include young age at diagnosis, female sex, chest radiation, and presence of cardiovascular risk factors (diabetes, hypertension, dyslipidemia, obesity, and smoking). In a recent large study on 2440 patients 28 treated with anthracyclines the cumulative 5‐year risk of cardiac heart failure (CHF) with all‐cause mortality as competing risk was 4.6% after 3 to 5 cycles of R‐CHOP, 4.5% after 6 and 7.9% after more than 6 cycles. Cumulative 5‐year risk for patients treated without anthracyclines was 0.8%.…”

Precision medicine in follicular lymphoma: Focus on predictive biomarkers

“…Use of anthracyclines is associated with increased risk of neutropenia, alopecia and delayed cardiotoxicity and ischemic heart disease 49,52 than some potential alternatives, such as RCVP or rituximab monotherapy, but it offers a longer PFS 8 . However, patients homozygous for the GG variant (rs1799977) of the MLH1 gene (about 8% of patients) do not benefit from the addition of doxorubicin to the treatment 36 .…”

Cardiotoxicity and Cardiac Monitoring Among Anthracycline-Treated Cancer Patients: A Retrospective Cohort Study

“… 11 Studies suggest that subjects with certain risk factors are more susceptible to anthracyclines-induced cardiotoxicity. 12–15 One of the main risk factors is the cumulative dose of anthracyclines, especially doxorubicin, in doses more than 400 mg/m2. 12 , 13 Other risk factors include age, smoking, obesity (ie, body mass index above 30), and the presence of cardiovascular diseases.…”

“… 12–15 One of the main risk factors is the cumulative dose of anthracyclines, especially doxorubicin, in doses more than 400 mg/m2. 12 , 13 Other risk factors include age, smoking, obesity (ie, body mass index above 30), and the presence of cardiovascular diseases. 14 , 15 Previous exposure to cardiotoxic agents or coadministration of chemotherapy that have cardiac adverse effects can also increase the risk of anthracycline-induced cardiotoxicity.…”