Cardiotoxicity in ibrutinib-treated patients: incidence, management, and impact on treatment outcomes

Introduction Ibrutinib, a Bruton's tyrosine kinase inhibitor, has revolutionized treatment for various hematologic malignancies but is associated with cardiovascular toxicities (CTR-CVT), particularly atrial fibrillation (AF) and hypertension (HTN). Understanding the incidence, severity, and clinical impact of CTR-CVT is critical for optimizing treatment and improving patient outcomes. Methods We retrospectively evaluated a cohort of patients treated with ibrutinib in a single tertiary center. Results 54 pts (41% female) with a mean age of 68 ± 12 years were included in the analysis. 18 pts (33%) developed CTR-CVT during a median follow-up of 15 (IQR: 5-34) months, with a median time to cardiotoxicity of 10 (IQR: 1-19) months. There were 6 pts (13%) with new onset/worsening HTN, 10 pts (10%) with new-onset AF, and 6 pts (13%) with new onset/worsening heart failure (HF). Regarding risk factors for CTR-CVT, HTN, smoking, and previous HF were more frequent in the CTR-CVT group (78% vs 36%, p = 0.008; 22% vs 3%, p = 0.010; 28% vs 3%, p = 0.013, respectively). AF occurred in a median of 8 (IQR: 1, 25) months after treatment initiation, with most of the cases (7 – 70%) being asymptomatic, and 2 (20%) requiring emergency hospital admission. Despite a mean CHA2DS2-VASc score of 3 ± 2, only 4 pts (40%) were started on oral anticoagulation, all with reduced doses. There were no thromboembolic or haemorrhagic events in this group. Considering other CTR-CVT, most events were mild, with 2 cases of CTCAE-grade >2 HTN and 1 case of grade 3 HF. 17 pts (32%) suspended ibrutinib after a median of 8 (IQR: 4, 19) months, with only 2 cases directly attributable to CTR-CVT. Kaplan-Meier analysis showed no significant differences between the groups regarding time to suspension of ibrutinib over 24 months (Log-rank p=0.089). 20 pts (37%) died during follow-up, with a median time to death from ibrutinib initiation of 11 (IQR: 4,26) months, but there were no statistically significant differences between the groups regarding overall mortality over 24 months (Log-Rank p = 0.209). Conclusions Cardiotoxicity was a common occurrence in our cohort of pts treated with ibrutinib, with AF being the most frequent event. Despite its prevalence, most cardiotoxic events were mild and manageable and not associated with a shorter time to suspension of ibrutinib (p = 0.089) or with greater overall mortality (p = 0.209).