INTRODUCTION: Unanticipated cardiotoxicity is now identified as a significant clinical problem associated with new anti-cancer targeted agents. Risk factors and natural history are still poorly understood. We aim to determine potential clinical risk factors for cardiotoxicity among patients with hematologic malignancies (HM) who were treated with targeted therapies over a 10-year period.
METHODS: We used 114 diagnosis codes for HM and 17 codes for cardiac diseases in order to identify patients in our electronic medical records (EPIC) and identify patients with HM who met above criteria. Cardiotoxicity was defined mainly by left ventricular ejection fraction (LVEF) of < 50%, arrhythmias, or ischemic cardiovascular event that occurred after initiation of the drug of interest. The targeted agents of interest include tyrosine kinase inhibitors (TKIs), proteasome inhibitors, monoclonal antibodies, hypomethylating agents, and immunomodulatory agents. Multivariable logistic regression was performed to estimate the odds ratios (ORs) and 95% confidence intervals (95% CI) of the potential risk factors. Kaplan-Meier analysis and log-rank test were used to evaluate the effect of cardiotoxicity on the overall survival of the patients.
RESULTS: Of 820 patients with both HM and cardiac diagnosis, 29 patients developed cardiotoxicity after initiation of targeted therapies. We selected 70 matched controls based on type of targeted therapy. In the study group, the median time from exposure to cardiac event was 120 days (range, 1-1176). Significantly higher number of patients had prior exposure to anthracyclines in study versus control group (65.5% vs 42.8%, P=0.04), however, this was not significant in multivariable analysis. Multiple other variables, including traditional risk factors for heart disease, were analyzed and did not differ significantly between the two groups. Only two variables remained significant in the multivariable analysis, including prior history of DVT/PE (OR 4.88, 95% CI: 1.44-16.54, P=0.011), and Karnofsky score of ≥80% (OR 3.99, 95% CI: 1.51-10.6, P= 0.005). With median follow-up of 27 months (range, 1-120), 17 patients in the study group died, but only 2 of cardiac causes. Repeat echocardiograms showed worsening of LVEF in 4 patients while stable/improved in 23 patients, and 21 patients were able to receive further chemotherapy. There was a trend towards worse overall survival in the study group (P= 0.071).
CONCLUSIONS: About 3.5% of patients with HM experience unanticipated cardiotoxicity due to targeted anti-cancer agents with related mortality of 6.8 %. Most patients do well with stable compensated cardiac function and 35% have an objective improvement in LVEF. Risk of cardiotoxicity was significantly higher in patients with known history of DVT/PE. Future studies of possible underlying genetic predisposition will be of great importance.
Citation Format: Chintan Shah, Yan Gong, Anita Szady, Qian Sun, carl J. Pepine, Taimour Langaee, Alexandra R. Lucas, Jan S. Moreb. Unanticipated cardiotoxicity due to targeted anti-cancer therapy in hematologic malignancies patients: Natural history and risk factors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 987. doi:10.1158/1538-7445.AM2017-987