A study presented at the 62nd ASH Annual Meeting & Exposition evaluated the risk of cardiovascular (CV) adverse events (AEs) in patients with chronic lymphocytic leukemia (CLL) treated with acalabrutinib. The researchers concluded that the risk was low and comparable to that of the general population with CLL.
Data were pooled from four studies—ACE-CL-001, ACE-CL-007 (ELEVANTE-TN), ACE-CL-309 (ASCEND), and 15-H-0016—with cutoff dates ranging from December 2018 to February 2019. The analysis included patients with CLL who received at least one dose of acalabrutinib monotherapy. Patients received oral acalabrutinib in daily doses ranging from 100 mg to 400 mg and later switched to twice daily 100 mg; treatment was continued until disease progression (PD) or toxicity.
A total of 762 patients (median age, 67 years; range, 32-89 years) were identified. There were 352 treatment-naïve patients (46%) and 410 relapsed/refractory patients (54%). Overall, 199 cardiac AEs of any grade—regardless of their association with treatment—were reported in 129 patients; seven patients discontinued treatment due to cardiac AEs. The most common AEs reported in ≥2% of patients were atrial fibrillation (afib, n=34; afib/flutter, n=38), palpitations (n=23), and tachycardia (n=17).
Prior to initiating acalabrutinib, 91% of patients with cardiac AEs (n=117/129) and 79% of patients without (n=503/633) had at least one CV risk factor. Among those who had cardiac AEs, the most common CV risk factors were hypertension (n=86), hyperlipidemia (n=38), and arrhythmias (n=29 [afib, n=16]).
Grade ≥3 cardiac AEs occurred in 37 patients (4%); these included afib (n=10), complete atrioventricular (AV) block (n=2), acute coronary syndrome (n=1), atrial flutter (n=1), second degree AV block (n=1), and ventricular fibrillation (n=1). Grade 5 AEs occurred in two patients: cardiac failure congestive and acute myocardial infarction. Just under half of the 37 patients with grade ≥3 cardiac AEs were continuing acalabrutinib at data cutoff (n=18); those who discontinued acalabrutinib did so due to the grade ≥3 cardiac AEs (n=6) or other AEs (n=4), PD (n=5), death (n=3), and other reasons (n=1). Sixteen of the 51 grade ≥3 cardiac AEs led to dose delay, and 36 were managed with concomitant medications; 43 of the events resolved.
Nearly half of patients who experienced any-grade cardiac AEs sustained them during the first six months of treatment. Of the 13 total grade ≥3 cardiac AEs, 25% were observed during this time; all AEs were managed with concomitant medications, except one grade 4 cardiac tamponade that required hospitalization. Two of the AEs led to treatment discontinuation.
A future study will compare the safety of acalabrutinib versus ibrutinib in patients with high-risk CLL, the study authors noted.