Age Range for Acalabrutinib Use in Clinical Trials
Acalabrutinib has been successfully used in clinical trials in patients up to 85 years of age, with no upper age limit established for its efficacy and safety. 1
Evidence from Clinical Trials
Relapsed/Refractory CLL Studies
The pivotal phase 1b/2 study in relapsed/refractory CLL enrolled patients with a median age of 66 years and an age range of 42-85 years, demonstrating that acalabrutinib maintained efficacy across this entire age spectrum. 1 This study showed an overall response rate of 94% with similar responses regardless of genomic features, and the estimated 45-month progression-free survival was 62%. 1
A more recent Chinese study in relapsed/refractory CLL included patients with a median age of 62 years, achieving an 85% overall response rate with 12-month and 18-month progression-free survival rates of 91.5% and 78.8%, respectively. 2
Treatment-Naive CLL Studies
In treatment-naive patients, the ACE-CL-001 trial enrolled patients with a median age of 64 years, achieving a 97% overall response rate with a 48-month duration of response rate of 97%. 3
The landmark ELEVATE-TN phase III study specifically enrolled patients **≥65 years or <65 years with coexisting conditions** (CIRS score >6 or creatinine clearance <70 mL/min), randomizing 535 patients to acalabrutinib-based regimens. 4 This study demonstrated 2-year progression-free survival rates of 93% for acalabrutinib plus obinutuzumab and 87% for acalabrutinib monotherapy, with 2-year overall survival rates of 95% in both acalabrutinib arms. 4
Oldest and Frailest Patient Population
The most compelling evidence comes from the CLL-Frail trial, which specifically enrolled patients ≥80 years old and/or frail patients, with a median age of 81 years. 5 This prospective trial demonstrated a 93.5% overall response rate, with estimated 12-month progression-free and overall survival rates of 93.3% and 95.7%, respectively. 5 Notably, 53.5% of patients reported improvement in their self-perceived frailty, and severe bleeding events were absent with only rare atrial fibrillation (two cases of grade 2 and 3). 5
Real-World Evidence
Real-world data from the French NAOS study included patients with a median age of 73 years in first-line and 77 years in relapsed/refractory settings, confirming effectiveness and safety consistent with clinical trials despite an older population with more cardiovascular comorbidities. 6 The 12-month real-world progression-free survival rate was 93.1% in first-line and 87% in relapsed/refractory patients. 6
Clinical Implications
No upper age limit has been established for acalabrutinib use based on clinical trial data, with successful treatment documented up to age 85 years in registration trials and a median age of 81 years in the dedicated frail/elderly population study. 1, 5
Acalabrutinib is particularly well-suited for older patients due to its favorable cardiovascular safety profile compared to ibrutinib, with lower rates of atrial fibrillation (4-7% overall, 1% grade ≥3) and hypertension (3-7% overall, 2-3% grade ≥3). 7, 4
The NCCN guidelines recommend acalabrutinib ± obinutuzumab for all patients with CLL without del(17p) or TP53 mutation, regardless of age, based on the ELEVATE-TN trial results. 4