PMID- 37957370
OWN - NLM
STAT- MEDLINE
DCOM- 20240122
LR  - 20240202
IS  - 1432-0584 (Electronic)
IS  - 0939-5555 (Linking)
VI  - 103
IP  - 2
DP  - 2024 Feb
TI  - Zanubrutinib-lenalidomide-rituximab (ZR(2)) in unfit diffuse large B-cell 
      lymphoma: efficient and tolerant.
PG  - 499-510
LID - 10.1007/s00277-023-05498-7 [doi]
AB  - The objective of this study is to examine the effectiveness and safety of 
      zanubrutinib, rituximab, and lenalidomide (ZR(2)) in unfit patients with diffuse 
      large B-cell lymphoma (DLBCL). Thrombosis or bleeding risk of ZR(2) regimen, 
      especially when antiplatelet agents were co-prescribed, was also evaluated. We 
      retrospectively reviewed unfit newly diagnosed (ND) and refractory or relapsed 
      (R/R) patients with DLBCL who were administered with ZR(2) regimen in two medical 
      centers between December 2019 and February 2022. Response rates, progression-free 
      survival (PFS), overall survival (OS), bleeding adverse events (AEs), and 
      thrombosis episodes were analyzed. Furthermore, we investigated the effects of 
      zanubrutinib alone or in combination with lenalidomide on platelet functions in 
      vitro and in vivo. A total of 30 unfit patients (13 ND DLBCL and 17 R/R DLBCL 
      patients) who received ZR(2) regimen were enrolled in the study (median age: 
      69.5 years). The ultimate ORRs for the ND DLBCL and R/R DLBCL were 77.0% and 
      50.1%, respectively. The median follow-up was 16.6 months. The median PFS and OS 
      were not achieved during the follow-up time. Subcutaneous hemorrhage AEs occurred 
      in four cases, three cases suffered severe bleeding events, and thrombosis events 
      were observed in two patients. ZR(2) regimen inhibited platelet functions 
      (aggregation, clot retraction, spreading and activation) in vitro and in vivo 
      function testing especially in response to collagen. ZR(2) is an efficient 
      treatment option for unfit patients with DLBCL and could be well tolerated. 
      Notably, this regimen inhibited platelet functions. Antiplatelet agents should be 
      used with caution in patients treated with this regimen.
CI  - (c) 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, 
      part of Springer Nature.
FAU - Wang, Yawen
AU  - Wang Y
AD  - Department of Hematology, Zhongshan Hospital, Fudan University, Shanghai, China.
AD  - Department of Hematology, the Affiliated Hospital of Qingdao University, Qingdao, 
      Shandong, China.
FAU - Xu, Jiadai
AU  - Xu J
AD  - Department of Hematology, Zhongshan Hospital, Fudan University, Shanghai, China.
AD  - Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China.
FAU - Li, Panpan
AU  - Li P
AD  - Department of Hematology, Zhongshan Hospital, Fudan University, Shanghai, China.
AD  - Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China.
FAU - Xu, Yanyan
AU  - Xu Y
AD  - Department of Biochemistry and Molecular Cell Biology, Shanghai Jiao Tong 
      University School of Medicine, Shanghai, China.
FAU - Xue, Hongwei
AU  - Xue H
AD  - Department of Hematology, the Affiliated Hospital of Qingdao University, Qingdao, 
      Shandong, China. hwx326@sina.com.
FAU - Liu, Peng
AU  - Liu P
AUID- ORCID: 0000-0002-9639-6606
AD  - Department of Hematology, Zhongshan Hospital, Fudan University, Shanghai, China. 
      liu.peng@zs-hospital.sh.cn.
AD  - Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China. 
      liu.peng@zs-hospital.sh.cn.
LA  - eng
GR  - 82100215/National Natural Science Foundation of China/
GR  - 22ZR1411400/Natural Science Foundation of Shanghai/
GR  - QDFYQN 202101009/Youth Foundation of the Affiliated Hospital of Qingdao 
      University/
GR  - GH000027/Cancer Research Foundation of Huiyu Pharmaceutical/
PT  - Journal Article
DEP - 20231114
PL  - Germany
TA  - Ann Hematol
JT  - Annals of hematology
JID - 9107334
RN  - F0P408N6V4 (Lenalidomide)
RN  - 4F4X42SYQ6 (Rituximab)
RN  - AG9MHG098Z (zanubrutinib)
RN  - 4Z8R6ORS6L (Thalidomide)
RN  - 0 (Platelet Aggregation Inhibitors)
RN  - 0 (Piperidines)
RN  - 0 (Pyrazoles)
RN  - 0 (Pyrimidines)
SB  - IM
MH  - Humans
MH  - Aged
MH  - Lenalidomide/adverse effects
MH  - Rituximab
MH  - Thalidomide
MH  - Retrospective Studies
MH  - Platelet Aggregation Inhibitors/therapeutic use
MH  - *Lymphoma, Large B-Cell, Diffuse/pathology
MH  - Antineoplastic Combined Chemotherapy Protocols/adverse effects
MH  - *Thrombosis/etiology
MH  - *Piperidines
MH  - *Pyrazoles
MH  - *Pyrimidines
OTO - NOTNLM
OT  - Bleeding events
OT  - DLBCL
OT  - Lenalidomide
OT  - Platelet functions
OT  - Unfit
OT  - Zanubrutinib
EDAT- 2023/11/14 00:42
MHDA- 2024/01/22 06:41
CRDT- 2023/11/13 23:41
PHST- 2023/07/05 00:00 [received]
PHST- 2023/10/06 00:00 [accepted]
PHST- 2024/01/22 06:41 [medline]
PHST- 2023/11/14 00:42 [pubmed]
PHST- 2023/11/13 23:41 [entrez]
AID - 10.1007/s00277-023-05498-7 [pii]
AID - 10.1007/s00277-023-05498-7 [doi]
PST - ppublish
SO  - Ann Hematol. 2024 Feb;103(2):499-510. doi: 10.1007/s00277-023-05498-7. Epub 2023 
      Nov 14.