Cardiovascular disease risk after radiotherapy and anthracycline-based chemotherapy for diffuse large B-cell lymphoma.

[BACKGROUND] Few studies examined treatment-specific long-term risks of cardiovascular diseases (CVD) in diffuse large B-cell lymphoma (DLBCL) survivors treated with potentially cardiotoxic radiotherapy and/or chemotherapy with/without rituximab after the 1990s.

[METHODS] Long-term CVD risk was examined in a multicenter cohort comprising 2,356 ≥ 5-year DLBCL survivors treated at ages 15 to 61 years in 1989 to 2012. CVD data were acquired from medical records, general practitioners and disease-registries. Observed CVD-numbers were compared with expected CVD-incidence in the Dutch population to estimate standardized incidence ratios (SIRs) and absolute excess risks (AERs/10,000 person-years). Treatment-specific CVD risks were assessed using multivariable Cox regression.

[RESULTS] During a median follow-up of 14.2 years (IQR 10.1 to 18.9), 312 survivors were diagnosed with a first CVD ≥5 years after treatment. Compared with the general population, DLBCL survivors had increased risks of heart failure ([HF], SIR 3.9, 95%CI 3.4-4.6, AER 62.8) and cerebrovascular accident (SIR 1.3, 95%CI 1.0 to 1.7, AER 9.8), while risk of coronary artery disease was decreased (SIR 0.7, 95%CI 0.5-0.9, AER -30.9). HF risk was higher among females (SIR 5.3, 95%CI 4.2 to 6.5) than males (SIR 3.2, 95%CI 2.6-4.0, P  heterogeneity<0.001), and among survivors ≤40 years at DLBCL treatment (SIR 10.5, 95%CI 7.2 to 14.8, P  trend<0.001). Exposure to > 300 mg/m2 doxorubicin was associated with a 2.8-fold (95%CI 1.7-4.5) increased risk of cardiomyopathy/HF, while radiotherapy involving the heart was associated with a 1.9-fold (95%CI 1.1 to 3.1) increased risk of valvular heart disease.

[CONCLUSION] ≥5-year DLBCL survivors have increased risks of developing CVDs, especially HF. Physicians and patients should recognize this risk, and individualized cardiac screening should be considered.