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 survivors treated with potentially cardiotoxic radiotherapy and/or chemotherapy with or without rituximab after the 1990s. METHODS: Long-term CVD risk was examined in a multicenter cohort comprising 2356 diffuse large B-cell lymphoma survivors who survived at least 5 years and who were treated at ages 15-61 years in 1989-2012. 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 (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 = 10.1-18.9 years), 312 survivors were diagnosed with a first CVD at least 5 years after treatment. Compared with the general population, diffuse large B-cell lymphoma survivors had increased risks of heart failure ([HF]; SIR = 3.9, 95% confidence interval [CI] = 3.4 to 4.6; absolute excess risk = 62.8) and cerebrovascular accident (SIR = 1.3, 95% CI = 1.0 to 1.7; absolute excess risk = 9.8), while risk of coronary artery disease was decreased (SIR = 0.7, 95% CI = 0.5 to 0.9; absolute excess risk = -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 to 4.0, P for heterogeneity < .001), and among survivors aged 40 years and younger at diffuse large B-cell lymphoma treatment (SIR = 10.5, 95% CI = 7.2 to 14.8; P for trend < .001). Exposure to more than 300 mg/m2 doxorubicin was associated with a 2.8-fold (95% CI = 1.7 to 4.5) increased risk of cardiomyopathy or 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: Those surviving at least 5 years after diffuse large B-cell lymphoma have increased risks of developing CVDs, especially HF. Physicians and patients should recognize this risk, and individualized cardiac screening should be considered.