Yan Zhang: Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College, Beijing, China.
Yanan Li: Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College, Beijing, China.
Zhe Zhuang: Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College, Beijing, China.
Wei Wang: Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College, Beijing, China.
Chong Wei: Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College, Beijing, China.
Danqing Zhao: Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College, Beijing, China.
Daobin Zhou: Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College, Beijing, China.
Wei Zhang: Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College, Beijing, China.
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.
