(A-118) Comparative Efficacy and Safety of Acalabrutinib Monotherapy in Chronic Lymphocytic Leukemia: A Systematic Review and Meta-Analysis

Background: Chronic lymphocytic leukemia (CLL) is a common malignancy in adults, with a variable clinical course and a high risk of immune dysfunction and secondary cancers. Bruton's tyrosine kinase (BTK) inhibitors, particularly acalabrutinib, have being considered as a promising treatment for CLL, especially in patients of high-risk genetic aberrations.

Objectives: This meta-analysis evaluates the comparative efficacy and safety of acalabrutinib monotherapy in CLL patients across randomized controlled trials (RCTs).

Methods: A comprehensive systematic review of RCTs comparing acalabrutinib monotherapy to control treatments in CLL patients was undertaken. A comprehensive search was carried out across PubMed, Embase, and Scopus databases. Data on efficacy endpoints, such as progression-free survival (PFS) and overall survival (OS), as well as treatment-emergent adverse events (TEAEs), were extracted. Random-effects models were used to generate hazard ratios (HR) for efficacy outcomes and TEAE associated risk ratios (RR).

Results: A total of three RCTs, involving 1199 patients, met inclusion criteria. Acalabrutinib monotherapy significantly improved OS compared to control treatments (HR = 0.7460, 95% CI: 0.5842 to 0.9525, p = 0.0188). However, the effect on PFS was marginally non-significant (HR = 0.3868, 95% CI: 0.1471 to 1.0168, p = 0.0541). The safety profile of acalabrutinib showed a lower incidence of severe neutropenia compared to controls, but higher rates of anemia and pneumonia. Acalabrutinib also exhibited an increased risk of cardiac events, though this was not statistically significant

Conclusions: Acalabrutinib monotherapy offers significant survival benefits over control treatments in CLL, with a generally favourable safety profile. However, concerns regarding anemia, pneumonia, and cardiac events highlight the need for careful monitoring in clinical practice. These findings support acalabrutinib as an effective treatment option, particularly for patients with high-risk CLL. Further studies are needed to address long-term safety and optimal combination strategies.