In CLL/SLL, zanubrutinib may have less cardiac impact than ibrutinib and acalabrutinib/acalabrutinib

Patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) treated with ibrutinib or acalabrutinib had a higher incidence of cardiovascular adverse events (AEs) compared with those treated with zanubrutinib, according to results of a recent study. Results of a real-world analysis of first-line BTK inhibitor treatment patterns in U.S. patients have been published.

A total of2465 patients who had previously received ibrutinib (n=1314), acotinib (n=1068) or zanubrutinib (n=83) were included in the retrospective analysis. Among patients who were followed for at least 3 months after treatment with a BTK inhibitor, patients treated with ibrutinib had the highest rate of cardiac adverse events at 10.1% (n=106/1048), followed by acotinib and zanubrutinib at 7.3% each (acolitinib, n=56/767; zanubrutinib, n=5/69). Among patients followed for at least 6 months, the incidence of cardiovascular AEs was 13.4% (n=123/921) with ibrutinib, 9.8% (n=62/631) with acotinib, and 7.5% (n=3/40) with zanubrutinib.

It is important to note that, given that the U.S. Food and Drug Administration (FDA) approved zanubrutinib for the treatment of patients with CLL/SLL in January 2023, zanubrutinib had a relatively small sample size and limited follow-up in this retrospective study compared with ibrutinib and acotinib, which the study authors noted as potential limitations of this study. Regulators approved ibrutinib and acotinib for first-line treatment of patients with CLL in March 2016 and November 2019, respectively. In current National Comprehensive Cancer Network guidelines, the second-generation BTK inhibitors acotinib (with or without obinutuzumab) and zanubrutinib are listed as the preferred first-line treatment options for patients with CLL/SLL, along with venetoclax plus obinutuzumab. The first-generation BTK inhibitor ibrutinib is listed under other recommended regimens.

In this real-world study, researchers investigated the clinical characteristics, treatment patterns, and associated adverse events in patients with CLL/SLL who received 1 of 3 BTK inhibitors in the frontline setting. Eligible patients required at least 5 or more CLL/SLL visits compared with non-CLL/SLL patients, and all patients required 2 or more evaluation and management visits. The objectives of the analysis were to determine patient demographics and baseline characteristics; incidence of cardiac adverse events; time to next treatment (TTNT); and time to treatment discontinuation or death (TTD).

Researchers determined5911 patients initiated first-line therapy; 2465 patients received first-line therapy with a BTK inhibitor, while 3446 patients did not receive first-line therapy containing a BTK inhibitor. Among patients who did not receive a BTK inhibitor in the first line, 185 patients received a BTK inhibitor in the later period. 90.2% of patients in the ibrutinib group, 88.6% of patients in the acotinib group, and 85.2% of patients in the zanubrutinib group had an ECOG performance status of 0 or 1. The 3-month follow-up rates of ibrutinib, acotinib, and zanubrutinib were 79.7%, 71.8%, and 83.1%, respectively. The 6-month follow-up rates were 70.1%, 59.1% and 48.1% respectively, and the median follow-up times were 19.1 months (95% CI, 0.4-41.5), 13.1 months (95% CI, 0.1-40.4) and 7.4 months (95% CI, 1.4-26.6) respectively.

The main comorbidities seen were chronic lung disease, diabetes without chronic complications, diabetes with chronic complications, gastroesophageal reflux disease, gastrointestinal disease, renal disease, and iron deficiency anemia. Additionally, any cardiovascular comorbidity was observed in 16.1%, 16.7%, and 12% of patients treated with ibrutinib, acotinib, and zanubrutinib, respectively. Cardiovascular comorbidities include acute ischemic heart disease, atrial fibrillation, hemorrhage, cardiac arrest, arrhythmia, hypertension, myocardial infarction, stroke, ventricular tachyarrhythmia, atrial flutter, congestive heart failure, ischemic stroke (cerebral infarction), left ventricular dysfunction, ventricular tachycardia, and angina pectoris.

Concerning all patients who received BTK inhibitors in the first line, the distribution of treatment regimens showed that 53.3% of patients received ibrutinib, 43.3% received acotinib, and 3.4% received zanubrutinib. Among patients who received a BTK inhibitor after first-line non-BTK inhibitor therapy, 45.9% received ibrutinib, 42.7% acotinib, and 11.4% zanubrutinib.

Additional data showed that patients who received first-line zanubrutinib experienced an unreached median TTNT (NR; 95% CI, 12.6-NR), compared with 31.3 months (95% CI, 26.5-35.5) in the ibrutinib group and 35.8 months (95% CI, 31.8-NR) in the acotinib group.

In the first-line setting, the median TTD was 12.7 months (95% CI, 11.7-15.3) with ibrutinib, 15.7 months (95% CI, 12.0-20.4) with acotinib, and 12.9 months (95% CI, 10.3-NR) with zanubrutinib. In addition, zanubrutinib had the highest proportion of patients continuing treatment at 6 months and 12 months, at 72.3% and 61.4%, respectively, compared with 62.6% and 53.1% at 6 months and 12 months, respectively, for acotinib, and 62.3% and 51.9% at 6 months and 12 months, respectively, for ibrutinib.