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Zanubrutinib-lenalidomide-rituximab (ZR2) in unfit diffuse large B-cell lymphoma: efficient and tolerant.

Abstract
The objective of this study is to examine the effectiveness and safety of zanubrutinib, rituximab, and lenalidomide (ZR2) in unfit patients with diffuse large B-cell lymphoma (DLBCL). Thrombosis or bleeding risk of ZR2 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 ZR2 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 ZR2 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. ZR2 regimen inhibited platelet functions (aggregation, clot retraction, spreading and activation) in vitro and in vivo function testing especially in response to collagen. ZR2 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.
AuthorsYawen Wang, Jiadai Xu, Panpan Li, Yanyan Xu, Hongwei Xue, Peng Liu
JournalAnnals of hematology (Ann Hematol) Vol. 103 Issue 2 Pg. 499-510 (Feb 2024) ISSN: 1432-0584 [Electronic] Germany
PMID37957370 (Publication Type: Journal Article)
Copyright© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
Chemical References
  • Lenalidomide
  • Rituximab
  • zanubrutinib
  • Thalidomide
  • Platelet Aggregation Inhibitors
  • Piperidines
  • Pyrazoles
  • Pyrimidines
Topics
  • Humans
  • Aged
  • Lenalidomide (adverse effects)
  • Rituximab
  • Thalidomide
  • Retrospective Studies
  • Platelet Aggregation Inhibitors (therapeutic use)
  • Lymphoma, Large B-Cell, Diffuse (pathology)
  • Antineoplastic Combined Chemotherapy Protocols (adverse effects)
  • Thrombosis (etiology)
  • Piperidines
  • Pyrazoles
  • Pyrimidines

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