Unanticipated Cardiotoxicity Associated with Targeted Anticancer Therapy in Patients with Hematologic Malignancies Patients: Natural History and Risk Factors

• Published in: Cardiovascular toxicology Vol. 18; no. 2; pp. 184 - 191
• Main Authors: Shah, Chintan, Gong, Yan, Szady, Anita, Sun, Qian, Pepine, Carl J., Langaee, Taimour, Lucas, Alexandra R., Moreb, Jan S.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.04.2018; Springer; Springer Nature B.V
• Subjects: Adult; Aged; Aged, 80 and over; Anthracycline; Anthracyclines; Antineoplastic Agents - adverse effects; Biomedical and Life Sciences; Biomedicine; Blood cancer; Cancer; Cancer patients; Cancer therapies; Cardiology; Cardiotoxicity; Cardiovascular diseases; Carfilzomib; Chemotherapy; Female; Health aspects; Heart diseases; Heart Diseases - chemically induced; Heart Diseases - diagnosis; Heart Diseases - mortality; Heart Diseases - physiopathology; Hematologic Neoplasms - drug therapy; Hematologic Neoplasms - immunology; Hematologic Neoplasms - metabolism; Hematologic Neoplasms - mortality; Humans; Immunomodulation; Karnofsky Performance Status; Male; Medical research; Medicine, Experimental; Middle Aged; Molecular Targeted Therapy - adverse effects; Monoclonal antibodies; Multivariate analysis; Pharmacology/Toxicology; Proteasome inhibitors; Protein-tyrosine kinase; Pulmonary Embolism - complications; Retrospective Studies; Risk Factors; Time Factors; Treatment Outcome; Venous Thrombosis - complications; Targeted therapy; Hematologic malignancies; Cardiotoxicity
• ISSN: 1530-7905; 1559-0259; 1559-0259
• DOI: 10.1007/s12012-017-9429-8

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.