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First-Line Therapy for Chronic Lymphocytic Leukemia: Bruton Tyrosine Kinase or BCL2 or Both?

ABSTRACT: Novel therapies largely have replaced chemoimmunotherapy as optimal first-line treatment of chronic lymphocytic leukemia (CLL). Approved novel therapies for CLL in the first-line setting include Bruton tyrosine kinase inhibitors, ibrutinib and acalabrutinib, and the BCL2 inhibitor venetoclax. Each of these novel agents has its own unique attributes and they have not been compared head to head in randomized trials. This review summarizes the pivotal trials that led to the approval of novel agents and compares the features of each agent to guide treatment decisions in treatment-naïve CLL. Ongoing studies investigating combinations of novel agents in the first-line setting also are discussed.

SUBMITTER: Cherng HJ

PROVIDER: S-EPMC9185694 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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First-Line Therapy for Chronic Lymphocytic Leukemia: Bruton Tyrosine Kinase or BCL2 or Both?

Cherng Hua-Jay J HJ Jain Nitin N

Hematology/oncology clinics of North America 20210526 4

Novel therapies largely have replaced chemoimmunotherapy as optimal first-line treatment of chronic lymphocytic leukemia (CLL). Approved novel therapies for CLL in the first-line setting include Bruton tyrosine kinase inhibitors, ibrutinib and acalabrutinib, and the BCL2 inhibitor venetoclax. Each of these novel agents has its own unique attributes and they have not been compared head to head in randomized trials. This review summarizes the pivotal trials that led to the approval of novel agents ...[more]

PMID: 34174983

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Project description: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.

Dataset Information

First-Line Therapy for Chronic Lymphocytic Leukemia: Bruton Tyrosine Kinase or BCL2 or Both?

Publications

First-Line Therapy for Chronic Lymphocytic Leukemia: Bruton Tyrosine Kinase or BCL2 or Both?

Similar Datasets

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