A Prospective Clinical Study of Zanubrutinib Combined with R-CHOP Regimen in the Treatment of Newly Diagnosed Double Expression Diffuse Large B-Cell Lymphoma

Objective

To explore the efficacy and safety of Zanubrutinib combined with the R-CHOP regimen (ZR-CHOP) in the treatment of newly diagnosed diffuse large B-cell lymphoma with MYC/BCL2 double expression (DE-DLBCL).

Methods

This is a prospective single-arm clinical study. Patients aged 18-80 years with newly diagnosed DE-DLBCL were enrolled and treated with 6 cycles of ZR-CHOP plus 2 cycles of rituximab. The immunohistochemical criteria for DE-DLBCL are MYC expression of 40% or higher, and BCL2 expression of 50% or higher. High-grade B-cell lymphoma with MYC and BCL2 rearrangements was excluded. Treatment response was evaluated using PET/CT after 4 cycles and 6 cycles.

Results

From April 15, 2022, to July 25, 2024, 15 patients were enrolled in the study. The median age was 56 years (range 35-70), and 13 patients (86.7%) were female. At diagnosis, 9 patients (60.0%) were in Ann Arbor stage III-IV, 5 patients (33.3%) had an ECOG score of 2 or higher, and 5 patients (33.3%) had an IPI score of 3 or higher. Additionally, 6 patients (40.0%) presented with B symptoms, 5 patients (33.3%) had extra nodal involvement, and 10 patients (66.7%) had the non-GCB subtype. All 15 patients (100%) completed 4 cycles of treatment, and 13 patients (86.67%) completed 6 cycles of treatment. The overall response rate (ORR) was 100.0%, with 13 patients (86.67%) achieving complete response (CR) and 2 patients (13.33%) achieving partial response (PR). As of the follow-up date on July 25, 2024, the median follow-up duration was 15.8 months (range 4.0-27.8). The 1-year estimated PFS and overall survival (OS) rates were both 92.3%, while the 2-year estimated PFS and OS rates were 69.2% and 92.3% respectively. One patient relapsed after 18.9 months of induced remission, and one patient died from accident. Common adverse events of grade 3-4 included anemia (46.7%), leukopenia (40.0%), neutropenia (46.7%), thrombocytopenia (33.3%), and pulmonary infection (26.7%, all are grade 3). Febrile neutropenia, atrial fibrillation and severe bleeding were not observed.

Conclusion

Zanubrutinib combined with R-CHOP regimen demonstrates a significant efficacy and good safety in the treatment of newly diagnosed DE-DLBCL, warranting further exploration.

No relevant conflicts of interest to declare.