Zanubrutinib Plus R-CHOP Therapy Shows Promising Efficacy, Acceptable Safety Among Patients With DLBCL Harboring Specific Gene Subtypes
Key Clinical Summary
- Population and Design: Single-center phase 2 trial (Fudan University Shanghai Cancer Center) evaluated zanubrutinib + R-CHOP among 59 treatment-naïve DLBCL patients with genetic alterations (MYD88, CD79B, NOTCH1, TP53, or c-Myc translocations); median follow-up 27 mo.
- Efficacy: ORR 91.4%, CR 79.3%; 3-year PFS 82.2% and OS 89.1%. Patients with the MCD subtype (n=25) achieved the highest complete metabolic response (84%), suggesting enhanced benefit in this genetic subgroup.
- Safety: AEs in 55.9%, grade ≥ 3 in 18.6% (notably neutropenia, myelosuppression, leukopenia, thrombocytopenia); 6 deaths from progression. Findings show promising antitumor activity and acceptable tolerability, supporting further study of zanubrutinib and R-CHOP in molecularly defined high-risk DLBCL.
The addition of zanubrutinib to standard rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy demonstrates high response rates and favorable survival outcomes among treatment-naïve patients with diffuse large B-cell lymphoma (DLBCL) harboring certain genetic alterations.
These results will be presented by Qunling Zhang, MD, Fudan University Shangahi Cancer Center, Shanghai, China, at the 2025 American Society of Hematology (ASH) Annual Meeting & Exposition in Orlando, Florida.
Approximately one third of patients with DLBCL fail to respond to standard R-CHOP chemotherapy. However, the addition of BTK inhibitors such as, zanubrutinib, demonstrates promising clinical activity. Researchers conducted a single-center, phase II trial to determine the safety and efficacy of zanubrutinib with R-CHOP therapy among patients with DLBCL who have MYD88, CD79B, NOTCH1, TP53, or c-Myc gene translocation mutations.
The primary end point was 3-year progression-free survival (PFS), with secondary end points including objective response rate (ORR), 3-year event free survival (EFS), overall survival (OS), and safety.
Overall, 59 patients were treated with zanubrutinib plus R-CHOP therapy and 53 patients had a response. The ORR was 91.4%, and the complete response (CR) rate was 79.3%. At a median follow-up of 27 months the estimated 3-year PFS was 82.2% and the 3-year OS was 89.1%.
Patients identified as having the multi-cancer detection (MCD) subtype by LymphGen algorithm (n=25) demonstrated the highest complete metabolic response (CMR) rate at 84%.
In terms of safety, adverse events occurred among 55.9% of patients, with 18.6% experiencing grade ≥3 treatment-related adverse events. The most common grade ≥3 treatment-related adverse events were neutropenia (n=5), myelosuppression (n=4), leukopenia (n=2), and thrombocytopenia (n=1). Disease progression resulting in death occurred among 6 patients.
The researchers concluded, “the preliminary results of this phase [2] clinical trial have shown encouraging antitumor activity of R-CHOP combined with zanubrutinib in DLBCL patients harbouring MCD subtype.”
They added, “in addition, our findings also suggest an acceptable safety profile for the combined regimens.”
Source:
Zhang Q, Juang S, Liu Y, et al. The phase II study of zanubrutinib combined with R-CHOP in previously untreated diffuse large B-cell lymphoma (DLBCL) patients with specific gene-expression. Dec 6-9, 2025; Orlando, FL. Abstract: 57
