INTRODUCTION: Unanticipated cardiac toxicity has been reported with anti cancer targeted and biological treatments. In this retrospective study, we aim at identifying the number of cardiac toxicity cases among patients with hematologic malignancies (HM) who were treated with targeted therapies over 10-year period with emphasis on natural history and outcomes.

METHODS: With the help of the Faculty Practice Decision Support (FPDS) team, we used 114 diagnosis codes for HM and 17 codes for cardiac diseases in order to mine our electronic medical records (EPIC) and identify patients with HM and specific cardiac problems, then sorted them according to whether they received known biologic agents such as thymidine kinase inhibitors (TKIs), proteasome inhibitors, monoclonal antibodies, hypomethylating agents, and immunomodulatory drugs.

RESULTS: FPDS team provided us with a file that contained medical records of 820 patients that had both HM and cardiac abnormalities. We pulled out 53 patients who received the drugs of interest. We were able to confirm cardiac toxicity defined mainly by left ventricular ejection fraction (LVEF) of < 50%, arrhythmias, or ischemic cardiovascular event in 44 patients. Ten patients were excluded because of pre-existing cardiac disease. Thus the final analysis was performed on the remaining 34 patients. The median follow-up was 9 mo (range, 1-78). The median age of this group was 66 years (range, 27-81), male/female 19/15, 26 Caucasians, and 15 were still alive. The median time from exposure to development of cardiac events was 120 days (range, <1-300). The diagnosis distribution was as follows: multiple myeloma 16, B-cell non-Hodgkin's lymphoma (NHL) 10, follicular NHL 4, Philadelphia positive acute lymphoblastic leukemia 3, MDS 1. Number of patients (n) who received suspected drugs contributing to the cardiac toxicity: bortezomib (8), carfilzomib (4), imatinib (2), dasatinib (4), Rituximab (13), and lenalidomide (3). Twenty one patients had no prior cardiac disease, while 11 had known coronary artery disease and 2 had known arrhythmias, while only 9 had no chronic co-morbidities. Fourteen patients did not receive anthracyclines including 2 who received rituximab. Nine patients had elevation in troponin and were diagnosed with NSTE myocardial infarction at the time of cardiac toxicity. Among the 19 dead patients, only 6 died of cardiac causes, while the rest died of their cancers. Repeat echocardiograms showed worsening of LVEF in 5 patients and improvement in 15 patients.

CONCLUSIONS: About 4.1% of patients with HM experience unanticipated cardiac toxicity with related mortality of 17.6%. Most patients do well with stable compensated cardiac function with objective improvement in LVEF. Whether Rituximab can cause cardiac toxicity is controversial and we will present specific arguments.

Citation Format: Jan S. Moreb, Haneen Mohammad, Lindsay McCullough, Anita Szady, Leslie Pettiford, Alexandra Lucas. Incidence and natural history of cardiovascular toxicity associated with biologic and targeted therapies used in hematologic malignancies. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1431.