In:
Blood, American Society of Hematology, Vol. 138, No. Supplement 1 ( 2021-11-05), p. 4556-4556
Abstract:
Background: Zanubrutinib is a second-generation Bruton's tyrosine kinase (BTK) inhibitor. The safety and efficacy of zanubrutinib in CNS lymphoma are unknown, as well as its brain distribution through the blood-brain barrier. Objective: A retrospective study of zanubrutinib-containing regimens was performed in patients with DLBCL to evaluate the efficacy of zanubrutinib. Paired plasma and cerebrospinal fluid (CSF) samples were collected to assess zanubrutinib's permeability through the BBB. Methods: Consecutive DLBCL patients treated with zanubrutinib-containing regimens from August to December 2020 in PUMCH were recruited. Paired plasma and CSF samples were collected at a fixed time point after zanubrutinib administration. Plasma and brain zanubrutinib quantification was performed by liquid chromatography-tandem mass spectrometry. Results: Totally 13 patients were enrolled, including primary CNS lymphoma (n=8) and systemic DLBCL (n=5). 53.8% (7/13) were refractory/relapsed, 84.6% (11/13) had CNS involvement. Overall response rates (ORRs) were 84.5% and 81.8% in the whole population and CNS involved cases, respectively. A total of 23 time-matched plasma-CSF sample pairs were collected. The mean peak concentration of zanubrutinib in the CSF was 2941.1 pg/ml (range, 466-9032.0). The corrected mean CSF/plasma ratio by protein binding of 94.0% was 42.7±27.7% (range, 8.6-106.3%), indicating the good penetrating ability through the BBB of free drug. The CSF/plasm ratio was not influenced by sex, DLBCL subtype, co-administrated BBB penetrating drugs or plasma drug concentration. Conclusion: This preliminary study revealed the efficacy of zanubrutinib-containing regimens in DLBLC, especially CNSL, for the first time. The excellent BBB penetration of zanubrutinib supports its further investigation in CNS lymphomas. Disclosures Li: Astellas Pharma, Inc.: Research Funding. OffLabel Disclosure: Zanubrutinib is a selective Bruton Tyrosine kinase(BTK) inhibitor and is approved for WM, MCL and CLL/SLL in the Unite States and China. BTK inhibitors such as ibrutinib and tirabrutinib are highly effective in CNS lymphoma and have good penetration ability of brain-blood-barrier. We supposed that zanubrutinib should be effective in DLBCL and CNS lymphomas just as other BTKi,so we prescribed zanubrutinib in this study.
Type of Medium:
Online Resource
ISSN:
0006-4971
,
1528-0020
DOI:
10.1182/blood-2021-150949
Language:
English
Publisher:
American Society of Hematology
Publication Date:
2021
detail.hit.zdb_id:
1468538-3
detail.hit.zdb_id:
80069-7
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