Dataset Information

Bruton tyrosine kinase inhibitors for the frontline treatment of chronic lymphocytic leukemia.

ABSTRACT: Chronic lymphocytic leukemia (cll) is the most commonly diagnosed adult leukemia in Canada. Biologic heterogeneity of cll between patients results in variable disease trajectories and responses to therapy. Notably, compared with patients lacking high-risk features, those with such features-such as deletions in chromosome 17p, aberrations in the TP53 gene, or unmutated immunoglobulin heavy chain variable region genes-experience inferior outcomes and responses to standard chemoimmunotherapy. Novel agents that target the B cell receptor signalling pathway, such as Bruton tyrosine kinase (btk) inhibitors, have demonstrated clinical efficacy and safety in patients with treatment-naïve cll, particularly those with high-risk features. However, given the current lack of head-to-head trials comparing btk inhibitors, selection of the optimal btk inhibitor for patients with cll is unclear and requires consideration of multiple factors. In the present review, we focus on the efficacy, safety, and pharmacologic features of the btk inhibitors that are approved or under clinical development, and we discuss the practical considerations for the use of those agents in the Canadian treatment landscape.

SUBMITTER: Banerji V

PROVIDER: S-EPMC7755444 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Bruton tyrosine kinase inhibitors for the frontline treatment of chronic lymphocytic leukemia.

Banerji V V Aw A A Robinson S S Doucette S S Christofides A A Sehn L H LH

Current oncology (Toronto, Ont.) 20201201 6

Chronic lymphocytic leukemia (cll) is the most commonly diagnosed adult leukemia in Canada. Biologic heterogeneity of cll between patients results in variable disease trajectories and responses to therapy. Notably, compared with patients lacking high-risk features, those with such features-such as deletions in chromosome 17p, aberrations in the <i>TP53</i> gene, or unmutated immunoglobulin heavy chain variable region genes-experience inferior outcomes and responses to standard chemoimmunotherapy ...[more]

PMID: 33380880

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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

Bruton tyrosine kinase inhibitors for the frontline treatment of chronic lymphocytic leukemia.

Publications

Bruton tyrosine kinase inhibitors for the frontline treatment of chronic lymphocytic leukemia.

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