Cargando…

Preliminary Evaluation of Zanubrutinib-Containing Regimens in DLBCL and the Cerebrospinal Fluid Distribution of Zanubrutinib: A 13-Case Series

Zanubrutinib is a second-generation Bruton’s tyrosine kinase inhibitor. Its safety and effectiveness in central nervous system (CNS) lymphoma along with its distribution in the brain and ability to cross the blood–brain barrier (BBB) remain unknown. This retrospective case series involved patients w...

Descripción completa

Detalles Bibliográficos
Autores principales: Zhang, Yan, Li, Yanan, Zhuang, Zhe, Wang, Wei, Wei, Chong, Zhao, Danqing, Zhou, Daobin, Zhang, Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8739956/
https://www.ncbi.nlm.nih.gov/pubmed/35004280
http://dx.doi.org/10.3389/fonc.2021.760405
_version_ 1784629211380580352
author Zhang, Yan
Li, Yanan
Zhuang, Zhe
Wang, Wei
Wei, Chong
Zhao, Danqing
Zhou, Daobin
Zhang, Wei
author_facet Zhang, Yan
Li, Yanan
Zhuang, Zhe
Wang, Wei
Wei, Chong
Zhao, Danqing
Zhou, Daobin
Zhang, Wei
author_sort Zhang, Yan
collection PubMed
description Zanubrutinib is a second-generation Bruton’s tyrosine kinase inhibitor. Its safety and effectiveness in central nervous system (CNS) lymphoma along with its distribution in the brain and ability to cross the blood–brain barrier (BBB) remain unknown. This retrospective case series involved patients with diffuse large B-cell lymphoma (DLBCL) treated with zanubrutinib-containing regimens from August to December 2020 in PUMCH. The amounts of zanubrutinib in the plasma and brain were assessed by liquid chromatography–tandem mass spectrometry in paired plasma and cerebrospinal fluid (CSF) samples. In total, 13 patients were included: eight primary CNS lymphoma cases and five systemic DLBCL cases with 61.5% (8/13) refractory/relapsed and 84.6% (11/13) showing CNS involvement. The overall response rates were 84.5% in the entire population and 81.8% in the CNS-involved cases. A total of 23 time-matched plasma-CSF sample pairs were collected. The mean peak concentration of zanubrutinib in CSF was 2941.1 pg/ml (range, 466–9032.0 pg/ml). The corrected mean CSF/plasma ratio determined based on 94% protein binding was 42.7% ± 27.7% (range, 8.6%–106.3%). This preliminary study revealed the effectiveness of zanubrutinib-containing regimens in DLBLC, especially CNS-involved cases, for the first time. The excellent BBB penetration of zanubrutinib supports its further investigation for the treatment of CNS lymphoma.
format Online
Article
Text
id pubmed-8739956
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-87399562022-01-08 Preliminary Evaluation of Zanubrutinib-Containing Regimens in DLBCL and the Cerebrospinal Fluid Distribution of Zanubrutinib: A 13-Case Series Zhang, Yan Li, Yanan Zhuang, Zhe Wang, Wei Wei, Chong Zhao, Danqing Zhou, Daobin Zhang, Wei Front Oncol Oncology Zanubrutinib is a second-generation Bruton’s tyrosine kinase inhibitor. Its safety and effectiveness in central nervous system (CNS) lymphoma along with its distribution in the brain and ability to cross the blood–brain barrier (BBB) remain unknown. This retrospective case series involved patients with diffuse large B-cell lymphoma (DLBCL) treated with zanubrutinib-containing regimens from August to December 2020 in PUMCH. The amounts of zanubrutinib in the plasma and brain were assessed by liquid chromatography–tandem mass spectrometry in paired plasma and cerebrospinal fluid (CSF) samples. In total, 13 patients were included: eight primary CNS lymphoma cases and five systemic DLBCL cases with 61.5% (8/13) refractory/relapsed and 84.6% (11/13) showing CNS involvement. The overall response rates were 84.5% in the entire population and 81.8% in the CNS-involved cases. A total of 23 time-matched plasma-CSF sample pairs were collected. The mean peak concentration of zanubrutinib in CSF was 2941.1 pg/ml (range, 466–9032.0 pg/ml). The corrected mean CSF/plasma ratio determined based on 94% protein binding was 42.7% ± 27.7% (range, 8.6%–106.3%). This preliminary study revealed the effectiveness of zanubrutinib-containing regimens in DLBLC, especially CNS-involved cases, for the first time. The excellent BBB penetration of zanubrutinib supports its further investigation for the treatment of CNS lymphoma. Frontiers Media S.A. 2021-12-24 /pmc/articles/PMC8739956/ /pubmed/35004280 http://dx.doi.org/10.3389/fonc.2021.760405 Text en Copyright © 2021 Zhang, Li, Zhuang, Wang, Wei, Zhao, Zhou and Zhang https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Zhang, Yan
Li, Yanan
Zhuang, Zhe
Wang, Wei
Wei, Chong
Zhao, Danqing
Zhou, Daobin
Zhang, Wei
Preliminary Evaluation of Zanubrutinib-Containing Regimens in DLBCL and the Cerebrospinal Fluid Distribution of Zanubrutinib: A 13-Case Series
title Preliminary Evaluation of Zanubrutinib-Containing Regimens in DLBCL and the Cerebrospinal Fluid Distribution of Zanubrutinib: A 13-Case Series
title_full Preliminary Evaluation of Zanubrutinib-Containing Regimens in DLBCL and the Cerebrospinal Fluid Distribution of Zanubrutinib: A 13-Case Series
title_fullStr Preliminary Evaluation of Zanubrutinib-Containing Regimens in DLBCL and the Cerebrospinal Fluid Distribution of Zanubrutinib: A 13-Case Series
title_full_unstemmed Preliminary Evaluation of Zanubrutinib-Containing Regimens in DLBCL and the Cerebrospinal Fluid Distribution of Zanubrutinib: A 13-Case Series
title_short Preliminary Evaluation of Zanubrutinib-Containing Regimens in DLBCL and the Cerebrospinal Fluid Distribution of Zanubrutinib: A 13-Case Series
title_sort preliminary evaluation of zanubrutinib-containing regimens in dlbcl and the cerebrospinal fluid distribution of zanubrutinib: a 13-case series
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8739956/
https://www.ncbi.nlm.nih.gov/pubmed/35004280
http://dx.doi.org/10.3389/fonc.2021.760405
work_keys_str_mv AT zhangyan preliminaryevaluationofzanubrutinibcontainingregimensindlbclandthecerebrospinalfluiddistributionofzanubrutiniba13caseseries
AT liyanan preliminaryevaluationofzanubrutinibcontainingregimensindlbclandthecerebrospinalfluiddistributionofzanubrutiniba13caseseries
AT zhuangzhe preliminaryevaluationofzanubrutinibcontainingregimensindlbclandthecerebrospinalfluiddistributionofzanubrutiniba13caseseries
AT wangwei preliminaryevaluationofzanubrutinibcontainingregimensindlbclandthecerebrospinalfluiddistributionofzanubrutiniba13caseseries
AT weichong preliminaryevaluationofzanubrutinibcontainingregimensindlbclandthecerebrospinalfluiddistributionofzanubrutiniba13caseseries
AT zhaodanqing preliminaryevaluationofzanubrutinibcontainingregimensindlbclandthecerebrospinalfluiddistributionofzanubrutiniba13caseseries
AT zhoudaobin preliminaryevaluationofzanubrutinibcontainingregimensindlbclandthecerebrospinalfluiddistributionofzanubrutiniba13caseseries
AT zhangwei preliminaryevaluationofzanubrutinibcontainingregimensindlbclandthecerebrospinalfluiddistributionofzanubrutiniba13caseseries