Findings on Cardiovascular Imaging in Patients Receiving Ibrutinib: Association With Cardiotoxicity

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In a study reported in JAMA Oncology, Buck et al found that myocardial injury detected on cardiovascular magnetic resonance imaging (CMR) was common in patients treated with ibrutinib and was associated with an increased risk of major adverse cardiac events.

Study Details

The study included data from consecutive patients receiving ibrutinib for cancer treatment who underwent evaluation with CMR between 2012 and 2019 from a large U.S. Comprehensive Cancer Center registry. The primary outcome measure was late gadolinium enhancement (LGE) fibrosis; a secondary outcome measure was occurrence of major adverse cardiac events (atrial fibrillation, heart failure, symptomatic ventricular arrhythmias, or sudden death) considered probably or definitely related to ibrutinib after CMR. CMR measures included myocardial native T1 and extracellular volume fraction for subclinical fibrosis, and max T2 for fibrosis and inflammation/edema. Measures were compared with those in a cohort of cardiovascular disease risk–matched cancer controls who did not receive ibrutinib.

Key Findings

A total of 49 patients treated with ibrutinib were identified, including 33 who underwent CMR after treatment initiation. Median duration of ibrutinib use was 14 months.

The mean (standard deviation [SD]) pretreatment values were 977.0 (73.0) ms for native T1 and 56.5 (4.0) ms for max-T2; four patients (13.3%) had LGE. After treatment initiation, mean (SD) values were 1,033.7 (48.2) ms for native T1 (P < .001 vs pretreatment) and 61.5 (4.8) ms for max-T2 (P = .01); 17 patients (54.8%) had LGE (P < .001).

After treatment initiation, elevated values (> 2 SDs) of CMR measures were observed in individual patients, with native T12SDs in 9 (28.6%) and max-T22SDs in 21 (63.0%). These measures were highest in patients with suspected ibrutinib toxic effects (P = .01 and P = .01, respectively).

No association was observed between traditional cardiovascular disease risk or cancer treatment status and abnormal CMR measures. Among ibrutinib-treated patients without traditional cardiovascular risk, 16 (58.6%) had LGE, compared with 13.3% of matched controls (relative risk = 4.8, P < .001).

Over a median follow-up of 19 months, 13 ibrutinib-treated patients (39.4%) experienced major adverse cardiac events. In multivariate analysis including traditional cardiovascular disease risk factors, LGE (hazard ratio [HR] = 4.9, P = .04) and native T12SDs (HR = 3.3, P = .05) were associated with increased risk of major adverse cardiac events.

The investigators concluded, “In this cohort study, myocardial injury was common in ibrutinib users, and its presence was associated with higher cardiotoxic risk.”

Daniel Addison, MD, of the Cardio-Oncology Program, The Ohio State University Medical Center, Columbus, is the corresponding author for the JAMA Oncology article.

Disclosure: For full disclosures of the study authors, visit

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