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.