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.