Meta-analysis of the efficacy and adverse effects of acalabrutinib in the management of relapsed/refractory chronic lymphocytic leukemia

Abstract

The advent of Bruton tyrosine kinase inhibitor (BTKi) therapy with ibrutinib introduced a highly effective targeted therapy in the management of chronic lymphocytic leukemia (CLL). However, due to the adverse effect profile some patients cannot tolerate this novel therapy. Newer, more potent and targeted BTK inhibitors such as acalabrutinib have been developed. Acalabrutinib is an irreversible and second generation BTKi that covalently inhibits BTK with greater selectivity than ibrutinib. As novel BTKis are developed, a greater understanding of their efficacy and adverse effect rates can assist clinicians and patients in the shared clinical decision-making process. A search was conducted using the PICOS model and PRISMA guidelines. PubMeb, Embase, and Cochrane Library databases were searched using the keywords: Acalabrutinib, Acalabrutinib Monotherapy, Tyrosine Kinase Inhibitor, and Relapsed/Refractory (R/R) CLL. After initial literature review 12 studies were chosen for evaluation in this meta-analysis. Meta-analysis and follow up meta-regression models were completed. The results were as follows: ORR 82% (95% CI 74%–90%, I² = 84.14%, p < 0.01), CR 4% (95% CI 2%–6%, I² = 0.00%, p = 0.99), mortality rate 12% (95% CI 6%–19%, I² = 87.23%, p < 0.01), mortality rate due to adverse effect 7% (95% CI 3%–10%, I² = 67.67%, p = 0.01), mortality due to pneumonia 2% (95% CI 1%–3%, I² = 0.00%, p = 0.43), mortality due to CLL progression 4% (95% CI 2%–6%, I² = 61.03%, p = 0.04), neutropenia (≥ grade 3) 18% (95% CI 15%–20%, I² = 0.00%, p = 0.70), thrombocytopenia (≥ grade 3) 7% (95% CI 4%–11%, I² = 54%, p = 0.09), anemia (≥ grade 3) 9% (95% CI 6%–12%, I² = 36.93%, p = 0.18), pneumonia (≥ grade 3) 10% (95% CI 6%–14%, I² = 66.37%, p = 0.02) and atrial fibrillation 7% (95% CI 3%–11%, I² = 80.13%, p = 0.00). The results demonstrate that acalabrutinib shows efficacy in the treatment of R/R CLL with tolerable adverse reaction rates.

Keywords:

• Acalabrutinib
• Bruton tyrosine kinase inhibitor
• BTKi
• relapsed/refractory chronic lymphocytic leukemia

Author contributions

D.P.: Literature review, manuscript concept, manuscript drafting, interpretation of data. A.C.: Statistical analysis, manuscript concept, manuscript editing, interpretation of data. Y.Y.: Statistical analysis, manuscript editing, interpretation of data. F.A.: Statistical analysis and interpretation of data. M.A.: Manuscript concept, manuscript editing, approved version to be published after critically revising intellectual content.

Data availability statement

The data that support the findings of this study are available on request from the corresponding author upon reasonable request.

Disclosure statement

The authors declare no conflicts of interest.

Additional information

Funding

No financial disclosures. No external funding sources utilized.