Real‐world effectiveness and safety of acalabrutinib in chronic lymphocytic leukaemia: Multicentre experience

Chronic lymphocytic leukaemia (CLL) primarily affects elderly patients with comorbidities, yet real-world data on acalabrutinib, a second-generation Bruton's Tyrosine Kinase (BTK) inhibitor, remain limited outside clinical trials, particularly in Italy. This retrospective multicentre study evaluated acalabrutinib monotherapy across 10 Italian haematology centres (2021–2025), including 155 adults with CLL/small lymphocytic lymphoma (SLL) (median age 74 years, 44.5% ≥75 years, 35.5% relapsed/refractory, 59.4% cardiovascular comorbidities, 24.5% del17p/TP53). Primary end-point was time-to-discontinuation (TTD ≥28 days interruption/progression/death); secondary included response rates (based on International Workshop on Chronic Lymphocytic Leukemia criteria), haematological recovery, overall survival (OS) and safety. Median TTD was not reached (16 months follow-up), overall response rate 84.5% (32.9% clinical complete remission, reinforced by bone marrow evaluation in four cases), OS median not reached (78.7% alive), reporting rapid haematological recovery occurred (at 6 months haemoglobin 11.1–12.6 g/dL, platelets 146–160 × 109/L, lymphocytes 57.5–12.3 × 109/L; p < 0.001), uniform across subgroups (no TTD differences by age/line/cardiovascular comorbidities/biology; p > 0.05), without reduction of neutrophils (p = 0.48). Discontinuation was 20% (primarily due to adverse events), with low cardiovascular toxicity (one grade 3 atrial fibrillation). This study confirms acalabrutinib's durable effectiveness and tolerability in unselected real-world CLL, above in patients with prior cardiovascular comorbidities, confirming clinical trial results also in frail elderly/high-risk patients, supporting its broad adoption in routine care.