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

Br J Haematol. 2018 Dec;183(5):717-726. doi: 10.1111/bjh.15603. Epub 2018 Nov 8.

Abstract

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.

Keywords: cardiology; chemotherapy; epidemiology; haemotoxicity; lymphomas.

Publication types

  • Comparative Study
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Anthracyclines / adverse effects*
  • Antibodies, Monoclonal, Murine-Derived / administration & dosage
  • Antibodies, Monoclonal, Murine-Derived / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Arrhythmias, Cardiac / chemically induced*
  • Arrhythmias, Cardiac / mortality
  • Cardiotoxicity / etiology
  • Cardiotoxicity / mortality
  • Cyclophosphamide / administration & dosage
  • Cyclophosphamide / adverse effects
  • Denmark / epidemiology
  • Doxorubicin / administration & dosage
  • Doxorubicin / adverse effects
  • Female
  • Heart Failure / chemically induced*
  • Heart Failure / mortality
  • Humans
  • Immunotherapy / adverse effects
  • Lymphoma, Follicular / drug therapy
  • Lymphoma, Follicular / mortality
  • Lymphoma, Large B-Cell, Diffuse / drug therapy
  • Lymphoma, Large B-Cell, Diffuse / mortality
  • Male
  • Middle Aged
  • Prednisone / administration & dosage
  • Prednisone / adverse effects
  • Registries
  • Retrospective Studies
  • Risk Factors
  • Rituximab
  • Vincristine / administration & dosage
  • Vincristine / adverse effects
  • Young Adult

Substances

  • Anthracyclines
  • Antibodies, Monoclonal, Murine-Derived
  • R-CHOP protocol
  • Rituximab
  • Vincristine
  • Doxorubicin
  • Cyclophosphamide
  • Prednisone