Efficacy and Safety of Bruton Tyrosine Kinase Inhibitor Monotherapy Compared with Combination Therapy for Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma: A Systematic Review and Meta-Analysis
by
, ,
Thi Thuy Nguyen
1,2,
Nguyen Thanh Nhu
1,3,
Van Khoi Tran
1,4,
Tran Thuc Huan Nguyen
2 and
Chiou-Feng Lin
5,6,7,* 1
International Ph.D. Program in Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan
2
Department of Oncology, Hue University of Medicine and Pharmacy, Hue University, Hue 49120, Vietnam
3
Faculty of Medicine, Can Tho University of Medicine and Pharmacy, Can Tho 94117, Vietnam
4
Department of Surgery, Hue University of Medicine and Pharmacy, Hue University, Hue 49120, Vietnam
5
Department of Microbiology and Immunology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan
6
Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, Taiwan
7
Core Laboratory of Immune Monitoring, Office of Research & Development, Taipei Medical University, Taipei 110, Taiwan
*
Author to whom correspondence should be addressed.
Cancers 2023, 15(7), 1996; https://doi.org/10.3390/cancers15071996
Submission received: 22 February 2023
/
Revised: 23 March 2023
/
Accepted: 23 March 2023
/
Published: 27 March 2023
(This article belongs to the Special Issue Targeted Drugs in Chronic Lymphocytic Leukemia)
Simple Summary
The approval of combination treatments such as chemoimmunotherapy was a breakthrough in managing chronic lymphocytic leukemia and small lymphocytic lymphoma (CLL/SLL) patients. However, benefits remain suboptimal. A Bruton tyrosine kinase inhibitor (BTKi) is an effective treatment for these patients. This meta-analysis reviewed published studies to compare the efficacy and safety of BTKis versus combination therapy in CLL/SLL. One thousand five hundred ten patients from four trials were analyzed. BTKi monotherapy was associated with significantly longer progression-free survival (PFS) and an improved overall response rate without excess toxicity. We observed similar benefits for PFS among patients with high-risk diseases. In addition, patients receiving second-generation BTKis (acalabrutinib or zanubrutinib) had fewer grade ≥ 3 adverse events than those receiving the combination treatment. Further studies are essential to enhance these results and determine the optimal therapy for managing CLL/SLL patients. This study may help hematologists plan the treatment of CLL/SLL.
Abstract
The effectiveness and safety of combination treatments such as chemoimmunotherapies in chronic lymphocytic leukemia and small lymphocytic lymphoma (CLL/SLL) remain controversial. Bruton tyrosine kinase inhibitors (BTKis) are an effective therapy for CLL/SLL patients. This meta-analysis aimed to compare the efficacy and safety of BTKis versus combination therapy in CLL/SLL patients. We searched the PubMed, Cochrane, Medline, and Embase databases through February 2023 for relevant randomized controlled trials (RCTs). Four RCTs (including 1510 patients) were found and met the inclusion criteria. Progression-free survival (PFS) was significantly improved with BTKis when compared to the combination therapy (hazard ratio (HR), 0.30; 95% confidence interval (CI), 0.22–0.40), while a pooled analysis of overall survival did not favor single-agent BTKis over the combination therapy (HR, 0.87; 95% CI, 0.67–1.15). We observed consistent benefits for PFS among patients with high-risk disease characteristics. Although there was no difference in complete response between the two arms (risk ratio (RR), 0.54; 95% CI, 0.20–1.46), BTKi use was related to a better overall response rate (RR, 1.10; 95% CI, 1.04–1.16). The risk of grade ≥3 adverse events (AEs) was comparable between the two arms (RR, 0.82; 95% CI, 0.55–1.23). However, the risk of grade ≥3 AEs was significantly lower in the second-generation BTKi group than in the combination therapy group (RR, 0.73; 95% CI, 0.54–0.98). Overall, BTKis have superior efficacy compared to the combination regimens in patients with untreated or treated CLL/SLL without excess toxicity. Further studies are needed to confirm these results and determine the optimal therapy for managing patients with CLL/SLL.
