Abstract
Relapsed and refractory (R/R) idiopathic multicentric Castleman disease (iMCD) is a clinical challenge with no standard treatment. In this preliminary clinical trial, we investigated the efficacy and safety profiles of a Bruton tyrosine kinase inhibitor (BTKi), zanubrutinib, in patients with R/R iMCD. The primary endpoint was the overall response rate at Week 12 according to the Castleman Disease Collaborative Network (CDCN) response criteria. The trial was terminated early due to a lack of treatment response in the first enrolled 5 patients. Although 3 patients achieved symptomatic response, none of the 5 patients had an overall response by Week 12. One patient had progressive disease and the other 4 had stable disease. The study drug was well tolerated without grade 2 or higher adverse events. Our findings suggest that BTKi therapy is not effective for iMCD, and further attempts at single-agent therapy with zanubrutinib or other BTKis for iMCD should be considered with caution and probably avoided. This trial was registered at www.clinialtrials.gov as #NCT04743687.
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Data availability
The data that support the findings of this study are available from the corresponding author (J.L.) upon reasonable request.
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Funding
This work was supported by the Research and Translation Application of Beijing Clinical Diagnostic Technologies Funds from Beijing Municipal Commission of Science and Technology [Grant No. Z211100002921016 [L.Z.]] and the National High Level Hospital Clinical Research Funding [2022-PUMCH-A-021[L.Z.]].
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J.L. and L.Z. designed the study. L.Z., Y.-H.G., S.-Y.L., H.Z., M.-Y.Z., Y.-Y.Y., Y.-T.L., and J.L. enrolled patients and collected data. L.Z. and Y.-H.G. interpreted the data and wrote the manuscript. H.Z. and S.-Y.L. prepared figures. All authors had access to primary data and gave final approval to submit for publication.
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Zhang, L., Gao, Yh., Li, Sy. et al. A prospective study of zanubrutinib, a Bruton tyrosine kinase inhibitor, in relapsed/refractory idiopathic multicentric Castleman disease. Int J Hematol (2024). https://doi.org/10.1007/s12185-024-03747-7
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DOI: https://doi.org/10.1007/s12185-024-03747-7