Zanubrutinib in Combination with R-CHOP for Previously Untreated Ｍcd Type of Diffuse Large B-Cell Lymphoma (DLBCL)
Authors: Yang Chunmei , Lu Ying , Wei Juying , Shou Lihong , Tong Hongyan , Jin Jie , Yu Wenjuan 
Published: December 2024

Introduction:
Patients with coexisting MYD88L265P and CD79B mutations (MCD subtype) of diffuse large B-cell lymphoma (DLBCL) exhibit poor outcomes with R-CHOP therapy, highlighting the urgent need for alternative treatment strategies. Numerous studies have demonstrated that MCD type of DLBCL is profoundly reliant on the B-cell receptor signaling pathway, and blocking Bruton's tyrosine kinase (BTK) can effectively disrupt this pathway, thereby eliciting an anti-lymphoma effect. The present study aimed to investigate the efficacy and safety of zanubrutinib in combination with R-CHOP in previously untreated DLBCL patients harboring both MYD88L265P and CD79B mutations. Herein, we present the preliminary findings of this investigation.
Methods ：
Previously untreated patients with coexisting MYD88L265P and CD79B mutations diffuse large B-cell lymphoma (MCD subtype of DLBCL), aged 18 to 70 years, with an ECOG performance status of 0 to 3, were enrolled in this study. Patients were administered with zanubrutinib (160 mg orally twice daily [BID]) plus R-CHOP chemotherapy（ZR-CHOP） for four consecutive 21-day cycles. Patients achieving complete remission (CR) after four cycles received an additional two cycles of ZR-CHOP, followed by two cycles of rituximab monotherapy. In contrast, patients assessed with a partial response (PR) after four cycles were prescribed an extended course of four additional ZR-CHOP cycles. The primary endpoint of the study was progression-free survival (PFS). Secondary endpoints encompassed the overall response rate (ORR)，overall survival（OS） and safety.
Results ：
Twenty-three patients with newly diagnosed MCD subtype of diffuse large B-cell lymphoma were enrolled until July 1, 2024. The median age was 59.5 years (range: 33-76 years). Twelve patients (52%) were assessed as stage III to IV according to the Ann Arbor staging system. Seventeen patients (73.9%) presented with extranodal involvement. Ten patients (43.5%) had an International Prognostic Index (IPI) score of 2 or higher. The cell of origin was germinal center B-cell (GCB) in 5 patients (21.7%) and non-GCB in 18 patients (78.3%).
At the data cut-off date of July 1, 2024, all 23 patients received at least one cycle of R-CHOP plus zanubrutinib. Fifteen patients had received 6 cycles of treatment, and 3 patients received 8 cycles. Among the 22 evaluable patients, ORR was 90.9%, with 19 patients (86.4%) achieving CR. One patient (4.5%) died due to progressive disease (PD), and another patient (4.5%) withdrew from the trial after completing 3 cycles due to disease progression. Among the 17 evaluable patients with the non-GCB subtype, 14 achieved CR, and 1 achieved PR.
The median follow-up time was 15.7 months (ranging from 4 to 28 months). The median PFS and OS had not been reached at the time of analysis. The estimated 1-year PFS rate was 90.2%, and the estimated 1-year OS rate was 94.1%. The ZR-CHOP regimen was generally well-tolerated.
Conclusions ：
Zanubrutinib in combination with the R-CHOP is effective and well-tolerated for previously untreated MCD subtype of Diffuse Large B-Cell Lymphoma.