Cardiotoxicity with Targeted Therapies Is Rare, but Requires Attention

TON - September 2017, Vol 10, No 5 - Conference Correspondent
Phoebe Starr

Washington, DC—Unanticipated cardiotoxicity occurs in an estimated 3.5% of patients with hematologic malignancies secondary to the use of targeted therapies, according to the results of a retrospective study presented at the 2017 Annual Meeting of the American Association for Cancer Research. In a multivariate analysis, a history of deep vein thrombosis or pulmonary embolism and a high Kar­nofsky score of ≥80% emerged as significant risk factors for cardiotoxicity (P = .011 and P = .005, respectively).

Although this is a small percentage of patients, the findings imply that oncologists and/or hematologists should collaborate with cardiologists to manage this toxicity when it occurs. Conventional risk factors for cardiac events do not seem to apply in this group of patients, with the exception of deep vein thrombosis or pulmonary embolism.

“It is surprising that patients with a high Karnofsky score were at greater risk for unanticipated cardiotoxicity, but patients with a low score probably received less chemotherapy. The underlying mechanisms that lead to cardiomyopathy could be the same ones that cause DVT/PE [deep vein thrombosis/pulmonary embolism],” said lead investigator Chintan Shah, MD, Assistant Professor, Division of Hospital Medicine, University of Florida, Gainesville.

Of 820 patients who met the International Classification of Diseases codes for hematologic malignancies treated with targeted therapy and a cardiac diagnosis (ie, left ventricular ejection fraction <50%, arrhythmias, or ischemic cardiac event), 29 had cardiac diagnoses after initiation of a targeted therapy.

Among these 29 patients (the study group), targeted therapies, such as rituximab (n = 10), multitargeted tyrosine kinase inhibitors (n = 3), immunomodulatory agents (n = 4), and proteasome inhibitors (n = 12) were used. Seventy matched controls were selected from the 820 patients based on type of targeted therapy. Both groups had comparable baseline demographics, including age, sex, race, body mass index, and hematologic malignancies. The control group had more men than the study group (62% vs 43%, respectively). Median time from exposure to cardiac event was 120 days (range, 1-1176 days).

At a median follow-up of 27 months (range, 1-120 months), 3.5% of patients developed cardiotoxicity related to targeted therapy, and 17 patients in the study group died—but only 2 (6.8%) of these deaths were caused by cardiac issues. Repeat echocardiograms showed worsening of left ventricular ejection fraction in 4 patients, whereas stable or improved results were observed in 23 patients; 21 patients were able to receive further chemotherapy. Median survival was 36 months for the study group (with cardiomyopathy), and 94 months for controls (with no cardiomyopathy), for an adjusted hazard ratio of 2.19 for mortality (95% confidence interval, 1.16-4.16; P = .016).

“Most patients do well, with stable or improved cardiac function, but overall survival was worse in this group. We strongly recommend collaborative efforts between the hematologist and/or oncologist and the cardiologist for optimal treatment of these toxicities,” Dr Shah told attendees.

Rituximab plus or minus other therapy was used in 10 of the 29 patients who developed cardiotoxicity. At least 4 patients had no exposure to anthracyclines, and most had normal ejection fractions prior to rituximab, but ejection fraction was lower after rituximab.

“The cardiotoxic potential of rituximab is not clear. Studies are conflicting,” Dr Shah concluded.

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Last modified: September 18, 2017