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Unanticipated Cardiotoxicity Associated with Targeted Anticancer Therapy in Patients with Hematologic Malignancies
Chintan Shah1, Yan Gong2,3, Anita Szady4
1Division of Hematology/Oncology, Department of Medicine, University of Florida, 1600 SW Archer Rd., PO Box 100277, Gainesville, FL, 32610, USA.
Insights
Unanticipated cardiotoxicity from targeted anticancer agents is rare but serious in hematologic malignancy patients. A history of DVT/PE is a key risk factor, impacting overall survival despite generally good cardiac outcomes.
Area of Science:
- Oncology
- Cardiology
- Pharmacology
Background:
- Anticancer targeted agents are increasingly used for hematologic malignancies (HM).
- Unanticipated cardiotoxicity is a significant concern but remains poorly understood.
- Cardiovascular diseases are common comorbidities in HM patients.
Purpose of the Study:
- To investigate the incidence and characteristics of unanticipated cardiotoxicity in HM patients treated with targeted agents.
- To identify risk factors and clinical outcomes associated with this cardiotoxicity.
Main Methods:
- Retrospective study of 820 HM patients with cardiovascular diseases using diagnosis codes.
- Defined cardiotoxicity per established criteria.
- Compared patients with cardiotoxicity (n=29) to 70 matched controls.
Main Results:
- Median time to cardiotoxicity was 132 days post-targeted therapy exposure.
- Prior deep vein thrombosis/pulmonary embolism (DVT/PE) and Karnofsky score ≥80% were significant predictors.
- Cardiotoxicity-related mortality was low (2/29), with most patients stabilizing or improving.
Conclusions:
- A small subset of HM patients experiences unanticipated cardiotoxicity with targeted agents, characterized by low mortality.
- History of DVT/PE is a significant risk factor for developing cardiotoxicity.
- Despite manageable cardiac events, overall survival (OS) is poorer in patients experiencing cardiotoxicity.
Abstract:
Our aim is to study unanticipated cardiotoxicity associated with the use of anticancer targeted agents, a problem that remains poorly understood. Using diagnosis codes, we retrospectively identified patients with both hematologic malignancies (HM) and cardiovascular diseases (n = 820 patients). Cardiotoxicity was defined per published criteria. The targeted agents of interest included tyrosine kinase inhibitors, proteasome inhibitors, monoclonal antibodies, and immunomodulatory agents. Patients found with cardiotoxicity (n = 29) were compared with 70 case-matched reference subjects. Median time from targeted therapy exposure to cardiotoxicity was 132 days. A higher percentage of patients had prior exposure to anthracyclines in study versus reference group (65.5 vs. 42.8%, P = 0.04), however, did not stay significant in multivariate analysis. Two variables were significant predictors, prior of DVT/PE and Karnofsky score of ≥ 80% (P ≤ 0.011). Only 2 study group patients died of cardiac causes. Most cardiotoxicity patients (23/29) had remained stable or improved, while 21 patients received further chemotherapy. OS was lower in the study group (P = 0.018) versus the reference group. In conclusion, a small number patients with HM experience unanticipated cardiotoxicity with low related mortality. Risk of cardiotoxicity was significantly associated with history of DVT/PE. Most patients do well, but despite that, their OS is significantly poorer.
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