Cumulative Anthracycline Exposure And Risk Of Cardiotoxicity; A Danish Nationwide Cohort Study Of 2440 Lymphoma Patients Treated With Or Without Anthracyclines

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.