Efficacy and safety of new-generation Bruton tyrosine kinase inhibitors in chronic lymphocytic leukemia/small lymphocytic lymphoma: a systematic review and meta-analysis

Shuo Yin; Xiaohong Zheng; Weichunbai Zhang; Hanyun Zhao; Rong Zhang; Wenbin Li; Feng Chen

doi:10.1007/s00277-023-05486-x

Efficacy and safety of new-generation Bruton tyrosine kinase inhibitors in chronic lymphocytic leukemia/small lymphocytic lymphoma: a systematic review and meta-analysis

Ann Hematol. 2023 Oct 16. doi: 10.1007/s00277-023-05486-x. Online ahead of print.

Authors

Shuo Yin¹, Xiaohong Zheng¹, Weichunbai Zhang¹, Hanyun Zhao¹, Rong Zhang¹, Wenbin Li², Feng Chen³

Affiliations

¹ Department of Neuro-Oncology, Cancer Center, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, China.
² Department of Neuro-Oncology, Cancer Center, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, China. liwenbin@ccmu.edu.cn.
³ Department of Neuro-Oncology, Cancer Center, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, China. chenfeng@bjtth.org.

PMID: 37843620
DOI: 10.1007/s00277-023-05486-x

Abstract

Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is a type of mature B lymphocyte clonal proliferative tumor with a specific immunophenotype. Bruton tyrosine kinase inhibitors (BTKi) have been approved for the treatment of CLL/SLL. However, the efficacy and safety of new-generation BTKi-based regimens have not been systematically studied. In this systematic review, we evaluated the efficacy and safety of new-generation BTKi-based regimens for the treatment of patients with CLL/SLL. A comprehensive search on PubMed, Embase, Cochrane Library, and ClinicalTrials.gov. up to January 31, 2023, was conducted by us. Studies reporting data on CLL/SLL patients treated with new-generation BTKi were included. We assessed the overall response rate (ORR), complete response (CR) rate, and 24-month OS/PFS rates for efficacy analysis. For safety analysis, we evaluated the incidence of grade ≥ 3 adverse events (AEs). The meta-analysis included twenty studies. The pooled ORR for new-generation BTKi was 92% (95% CI, 89-95%, I² = 80.68%, P = 0.00), while the pooled CR rate was 10% (95% CI, 6-14%, I² = 88.11%, P = 0.00). Research has found that the new-generation BTKi-based therapy had higher efficacy under the following treatment conditions: < 65 years old, treatment-naive (TN)-CLL, and BTKi combination therapy. The ORR/CR rates and 24-month OS/PFS rates of BTKi combination therapy were higher than that of BTKi monotherapy. Compared to acalabrutinib monotherapy, zanubrutinib monotherapy demonstrated higher ORR/CR rates and 24-month OS/PFS rates. Common grade ≥ 3 AEs included cytopenia and hypertension. The new-generation BTKi-based therapy has good tolerance and provides incremental benefits for CLL/SLL patients. Despite the superior efficacy of BTKi combination therapy compared to monotherapy, its AEs rates are relatively high. Compared to acalabrutinib, Zanubrutinib may be the preferred monotherapy for CLL. However, randomized-controlled studies are still needed.

Keywords: Bruton tyrosine kinase inhibitor; Chronic lymphocytic leukemia; Meta-analysis; Small lymphocytic lymphoma; Systematic review.

Publication types

Review