Abstract 4146837: Risk of Cardiac Events of New-generation versus Old-generation Bruton Tyrosine Kinase Inhibitors in Patients with Hematological Malignancies: A Systematic Review and Meta-analysis of RCTs

Background: Bruton Tyrosine Kinase inhibitors (BTKi) are targeted therapies that have demonstrated promising results in the treatment of hematological malignancies; however, they are associated with adverse cardiac events. Direct comparisons of the cardiotoxic profile between old-generation and new-generation BTKi are limited. Research Question: Are novel BTKi associated with a lower incidence of cardiac adverse events compared with ibrutinib? Aims: We aimed to perform a systematic review and meta-analysis of cardiac events from studies comparing new-generation BTKi versus ibrutinib in patients with hematological malignancies. Methods: We searched PubMed, Embase, and Cochrane Library for studies comparing any new-generation BTKi with ibrutinib in patients with hematological malignancies. Outcomes included 1) risk of cardiac events; 2) atrial fibrillation (AF); 3) rate of treatment discontinuations due to AF; and 4) hypertension. We pooled risk ratios (RR) with 95% confidence intervals (CI). Statistical analysis was performed using R software 4.3.1, under a random-effects model. Heterogeneity was assessed using I 2 statistics. Results: We included four randomized controlled trials with 1905 patients, of whom 957 (50%) received new-generation BTKi. Age ranged from 28 to 90 years, with 1337 (70%) male patients. Prior lines of systemic therapy ranged from none to 12. Overall cardiac events were significantly lower in patients who received novel BTKi compared with those who received ibrutinib (RR 0.75; 95% CI 0.63 to 0.90; p=0.002; I 2 =0%; Fig.1A). New-generation BTKis were associated with a statistically significant reduction in the risk of AF (RR 0.48; 95% 0.35 to 0.64; p<0.001; I2=0% Fig.1B) and treatment discontinuation due to AF (RR 0.07; 95% CI 0.01 to 0.34; p=0.001; I 2 =0%), compared with ibrutinib. However, there was no statistically significant reduction in the risk of hypertension with novel BTKi relative to ibrutinib (RR 0.58; 95% CI 0.34 to 1.01; p=0.053; I 2 =81%). Conclusion: Our findings suggest that treatment with new-generation BTKi is associated with a significant reduction in the risk of cardiac events, AF, and AF-related treatment discontinuation compared with the old-generation BTKi.