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

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.

Cardiotoxicity due to targeted anticancer agents: a growing challenge

“…17 Clinical evidence suggests that the cardiovascular toxicity of targeted agents seems to be reversible after discontinuation of therapy. 18,19 In our study, 14 as many as 79% of patients had stable to improved LVEF on follow up. However, our study still showed that the study group had a significantly worse OS compared with the reference group, with no difference in cancer progression-free survival between the two groups.…”

“…Moreover, significant uncertainty prevails in understanding the predisposing factors and the natural history of CVCs. In our retrospective study of patients, 14 who had both hematologic malignancy (multiple myeloma, leukemia, and lymphoma) and CVCs, we found that 3.5% (29 of 820) of patients experienced cardiotoxicity (study group) due to targeted agents (such as proteasome inhibitors, TKIs, anti CD20 rituximab, and immunomodulators) over the 10-year study period (2005–2014). The median time from the exposure to cardiac event was 132 days (range 1–1176 days).…”

Efficacy and safety of carfilzomib in relapsed and/or refractory multiple myeloma: systematic review and meta-analysis of 14 trials

“…It is recommended that patients receiving Carf be closely monitored for cardiac complications, however, proper monitoring strategy needs to be determined. Moreover, identifying predisposing factors for cardiotoxicity needs further research as traditional cardiovascular risk factors did not show any association in a retrospective analysis [ 36 ].…”

Antitumour Drug Induced Cardiovascular Toxicity and Current Tumour Treatment Methods

“…Ранние проявления кардиотоксичности возникают в течение 1 года, а поздние могут возникнуть спустя 7 лет после применения препаратов [7]. Чаще всего именно при применении антрациклиновых антибиотиков возникает нарушение фракции выброса левого желудочка [8]. Если произошло раннее выявление данного побочного эффекта, то высока вероятность того, что может произойти снижение или полное исчезновение сердечной патологии.…”