A prospective study of zanubrutinib, a Bruton tyrosine kinase inhibitor, in relapsed/refractory idiopathic multicentric Castleman disease

• DOI: 10.1007/s12185-024-03747-7
• Publication Date: 2024-03-28T06:02:01Z
• Authors: Lu Zhang; Yu-han Gao; Si-yuan Li; Hao Zhao; Miao-yan Zhang; Yan-ying Yu; Yan-ting Liu; Jian Li
• Keywords: Male; Adult; Castleman Disease; Tyrosine Kinase Inhibitors; Middle Aged; Pyrimidines; Treatment Outcome; Piperidines; Recurrence; Agammaglobulinaemia Tyrosine Kinase; Humans; Pyrazoles; Female; Prospective Studies; Protein Kinase Inhibitors; Aged

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.