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Pre-clinical Evaluation of Tyrosine Kinase Inhibitors for Treatment of Acute Leukemia
Published on: September 18, 2013
A Meta-analysis Investigating Response Rates with Continuous Bruton Tyrosine Kinase Inhibitor Monotherapies in the
Pier Luigi Zinzani1,2, Rhys Williams3, Mei Xue3
1IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia "Seràgnoli", Bologna, Italy.
Introduction:
Bruton tyrosine kinase inhibitor (BTKi) monotherapies have improved patient outcomes in B cell lymphomas; however, evidence on their comparative efficacy remains limited. This meta-analysis compared the efficacy of BTKi monotherapies across treatment naïve (TN) and/or relapsed and refractory (R/R) B cell lymphomas.
Methods:
Clinical trials reporting complete response (CR) or overall response rate (ORR) for zanubrutinib, acalabrutinib, or ibrutinib monotherapy in chronic lymphocytic leukemia (CLL), marginal zone lymphoma (MZL), mantle cell lymphoma (MCL), or Waldenström macroglobulinemia (WM) were included. Response rates from similar duration of follow-up were pooled across applicable studies. Naïve odds ratios (ORs) comparing CR and ORR of zanubrutinib with acalabrutinib or ibrutinib were calculated within each B cell lymphoma indication and then meta-analyzed across all indications using a random effects model.
Results:
The meta-analysis found zanubrutinib to be associated with statistically significant improvements in investigator-assessed CR and ORR vs acalabrutinib and ibrutinib across B cell lymphomas, using data with similar duration of follow-up. The pooled OR estimates [95% CI] for CR were 1.80 [1.03, 3.13] for zanubrutinib vs acalabrutinib and 2.85 [1.16, 7.04] for zanubrutinib vs ibrutinib across all B cell indications. ORs significantly favored zanubrutinib over acalabrutinib and ibrutinib for R/R MCL, and over ibrutinib for R/R MZL. The pooled OR estimates for ORR were 1.59 [1.00, 2.53] for zanubrutinib vs acalabrutinib and 2.25 [1.40, 3.61] for zanubrutinib vs ibrutinib. ORs significantly favored zanubrutinib over acalabrutinib and ibrutinib for TN CLL, and over ibrutinib for R/R MCL and R/R MZL.
Conclusion:
Consistent with the results of existing head-to-head trials, zanubrutinib demonstrated either numerically or statistically significant improved CR and ORR compared to acalabrutinib and ibrutinib across B cell lymphomas. Similar trends were observed within each indication. These findings suggest that zanubrutinib is the most effective BTKi treatment option for patients across B cell lymphomas.
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