Adjusted indirect comparison of zanubrutinib and ibrutinib in first-line treatment of chronic lymphocytic leukemia

• Published in: Farmacia hospitalaria : organo oficial de expresion cientifica de la Sociedad Espanola de Farmacia Hospitalaria Vol. 48; no. 1; p. 9
• Main Authors: Salmerón-Navas, Francisco Javier, Barreiro-Fernández, Ester María, Fénix-Caballero, Silvia
• Format: Journal Article
• Language: English
• Published: Spain 01.01.2024
• Subjects: Adenine; Humans; Leukemia, Lymphocytic, Chronic, B-Cell - drug therapy; Protein Kinase Inhibitors - adverse effects; Tyrosine Kinase Inhibitors; Chronic Lymphocytic Leukemias; Inhibidor tirosin cinasa de bruton; Leucemia linfocítica crónica; Alternativas terapéuticas equivalentes; Equivalent therapeutic alternatives; Bruton's tyrosine kinase inhibitors; Ibrutinib; Zanubrutinib
• ISSN: 2171-8695

The aim of this study was to perform an adjusted indirect treatment comparison, according to the cytogenetic profile, in terms of efficacy between different Bruton tyrosine kinase inhibitors used as first-line monotherapy for chronic lymphocytic leukemia. Safety outcomes considered of interest were also evaluated to establish whether these options can be considered equivalent therapeutic alternatives. A literature search was conducted in Pubmed and Embase on 10 November 2022 for phase III clinical trials studying Bruton's tyrosine kinase inhibitors in monotherapy in the first-line setting for CLL. Results were filtered according to whether the combination of bendamustine and rituximab was used as comparator and whether they had similar populations and follow-up times. Subgroup results were meta-analyzed according to mutational characteristics by classifying patients into high and low cytogenetic risk. An adjusted indirect comparison was developed using Bucher's method. Possible therapeutic equivalence was determined by applying the guide to equivalent therapeutic alternatives. Of the 39 studies obtained in the review, two clinical trials were selected: one for zanubrutinib and one for ibrutinib. The remaining studies were not included because they did not meet the inclusion criteria. The results obtained in the adjusted indirect treatment comparison for both cytogenetic risk subgroups showed no statistically significant differences. The most relevant safety differences were auricular fibrillation, hypertension and cardiovascular events in patients treated with ibrutinib and higher incidence of secondary cancers in patients treated with zanubrutinib. Applying the ATE guideline criteria, both treatments cannot be considered equivalent therapeutic alternatives. Assuming the uncertainty associated with the adjusted indirect comparison, zanubrutinib could be considered equivalent in efficacy to ibrutinib, however, the presence of differentiating safety features precludes assigning the two alternatives as equivalent therapeutic alternatives.