Zanubrutinib Plus Salvage Chemotherapy in Refractory/Relapsed Diffuse Large B-Cell Lymphoma Patients Non-Candidate for Autologous Stem Cell Transplantation: A Retrospective Study

Introduction：Salvage chemotherapy followed by autologous stem cell transplantation (auto-SCT) is effective for relapsed or refractory DLBCL (R/R DLBCL). However, many patients are unable to undergo auto-SCT due to age, comorbidities, tolerance, economy and other factors. R/R DLBCL has poor clinical outcomes when treated with conventional salvage chemotherapy. Zanubrutinib, a selective Bruton’s tyrosine kinase (BTK) inhibitor, has been shown to have modest antitumor activity in R/R DLBCL. Here we aimed to evaluate the efficacy and safety of Zanubrutinib plus salvage chemotherapy in autologous stem cell transplantation-ineligible R/R DLBCL patients.

Methods: We retrospectively reviewed R/R DLBCL patients who were administered with Zanubrutinib 160mg*bid plus BR （Bendamustine 90mg/㎡*d1-2+Rituximab 375mg/㎡*d0）or R2 （Lenalidomide 25mg* d1-21 +Rituximab 375mg/㎡*d0）in our center between January, 2019 and July, 2023.

Results: 49 R/R DLBCL patients were enrolled,including 30 patients in the Zanubrutinib plus BR group(ZBR)and19 patients in the Zanubrutinib plus R2 group(ZR2). Median age at this study was 60 years (range, 33-80). The best overall response rate (ORR) was 57.1% and complete remission rate was 12.2%. The ORR of ZBR group and ZR2 group were 63.2% and 53.3%, respectively. The response rate was lower in elderly, patients with ≥4 line treatment, refractory patients, patients with TP53 mutations, or without MYD88 and CD79A/B mutations. TThere was a positive correlation between the number of treatment cycles and ORR. With a median follow-up of 22 months (range, 6-43), the median progression-free survival (PFS) was 6.0 months, and the overall survival (OS) was 21.0 months. For OS, univariate analysis suggested that the number of treatment cycles was an independent favorable prognostic factor for OS. In multivariate analysis, , relapsed patients had better OS compared with refractory patients, and response after treatment was an independent favorable factor for OS. The most common grade-3/4 adverse events were neutropenia (55.0%), thrombocytopenia (44.9%), and pneumonia (30.1%).

Conclusion: Zanubrutinib combined with BR or R2 showed promising efficacy and acceptable safety in R/R DLBCL patients, which may be a potential treatment option for autologous stem cell transplantation-ineligible R/R DLBCL patients.