Abstract
Chronic lymphoid leukemia (CLL) is a common adult leukemia that has been treated with chemoimmunotherapy, which has significant toxicity among patients. Advances in CLL understanding have led to targeted therapies, such as Bruton's tyrosine kinase (BTK) inhibitors. Acalabrutinib is one of the second-generation BTK inhibitors and offers improved selectivity, reducing off-target effects. This systematic review and meta-analysis analyze data from multiple clinical trials to assess acalabrutinib efficacy and safety among patients with CLL. A literature search was carried out in PubMed, Cochrane Controlled Register of Trials (CENTRAL), MEDLINE (Medical Literature Analysis and Retrieval System Online), and Ovid databases for articles published until 2024. The outcomes included the overall response rate (ORR), complete response rate (CRR), 24-month progression-free survival rate, and grade ≥3 adverse events (AEs). Meta-analysis was performed using jamovi software. The search strategy yielded 823 records. After assessing the eligibility of the retrieved studies, the systematic review finally included six clinical trials, including 808 patients. The findings demonstrated significant efficacy of acalabrutinib, with a pooled ORR (P < 0.001) and a pooled CRR (P = 0.001). The pooled 24-month progression-free survival (PFS) rate showed a significant improvement in maintaining patient safety and treatment effectiveness (P <0.001). However, hematological AEs such as neutropenia, anemia, and thrombocytopenia were reported across studies. The pooled grade ≥ 3 AEs rate was 0.51 (95% CI: 0.21-0.81, I² = 98.21%, P <0.001), indicating a notable incidence of severe side effects. Acalabrutinib is an active drug in treating CLL that induces significant clinical benefits concerning response rates and PFS. However, acalabrutinib should be managed carefully to mitigate the risk of severe AEs. Further trials should be focused on assessing and modulating the safety of acalabrutinib.