-Author name in bold denotes the presenting author
-Asterisk * with author name denotes a Non-ASH member
Clinically Relevant Abstract denotes an abstract that is clinically relevant.

PhD Trainee denotes that this is a recommended PHD Trainee Session.

Ticketed Session denotes that this is a ticketed session.

4468 Zanubrutinib Combined with R-CHOP in Previously Untreated Non-Germinal Center B-Cell (GCB) Diffuse Large B-Cell Lymphoma (DLBCL) Patients with BCL2 and MYC Protein Co-Expression: A Multicenter, Phase II Study

Program: Oral and Poster Abstracts
Session: 626. Aggressive Lymphomas: Prospective Therapeutic Trials: Poster III
Hematology Disease Topics & Pathways:
Research, clinical trials, adult, Lymphomas, non-Hodgkin lymphoma, Clinical Research, Diseases, Therapies, Lymphoid Malignancies, Study Population, Human
Monday, December 11, 2023, 6:00 PM-8:00 PM

Jia Jin1*, Yalan Wang2*, Xi Wang2*, Yonghong Tang3*, Shan Zeng3*, Juan Du4 and Junning Cao5

1Department of Lymphoma, Fudan University Shanghai Cancer Center, Shanghai, AL, China
2Department of Lymphoma, Baotou Tumor Hospital, Baotou, Inner Mongolia, China
3Department of Internal Oncology, Xiangya Hospital of Central South University, Changsha, Hunan, China
4Department of Lymphoma, Shanghai Changzheng Hospital, Shanghai, China
5Department of Lymphoma, Fudan University Shanghai Cancer Center, Shanghai, China


DLBCL is the most common subtype of lymphoma, accounting for up to 40% of lymphoma cases worldwide and can be classified into GCB and non-GCB by immunohistochemistry (IHC). Rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy is the standard first-line treatment of DLBCL. Patients with non-GCB DLBCL or co-expression of BCL2 and MYC have a worse outcome with R-CHOP treatment. Previous study has showed that ibrutinib combined with R-CHOP had improved event free survival (EFS) compared with placebo plus R-CHOP in non-GCB DLBCL patients with BCL2 and MYC co-expression (Johnson et al., Blood 2019). This study aimed to investigate the efficacy and safety of the new-generation BTKi zanubrutinib combined with R-CHOP in previously untreated non-GCB DLBCL patients with BCL2 and MYC protein co-expression. Here, we report the preliminary results of this study.


Eligible patients were previously untreated non-GCB DLBCL confirmed by Hans’ algorithm,

age 18 years or older, MYC positive (defined as ≥40% of tumor cells showed any level of MYC nuclear staining above background) and BCL-2 positive (defined as ≥50% of tumor cells showed a cytoplasmic intensity score of 2+ or 3+) determined by IHC, and Eastern Cooperative Oncology Group performance status of 0-2.Patients were treated with R-CHOP combined with zanubrutinib (160 mg oral BID per day) of each 21-day cycle for six cycles. After 4 cycles, response was assessed by CT per Lugano 2014 criteria. Patients who were progression disease (PD) would discontinue the treatment. After completion of 6 cycles treatment, patients who were assessed with complete response (CR) (by PET-CT) would proceed to zanubrutinib (160 mg oral BID) maintenance treatment for one year, or until PD, intolerance of toxicity, loss of follow-up, withdrawal of informed consent, or death. Patients who were not CR would receive subsequent anti-tumor therapies determined by investigator. The primary endpoint was 3-year EFS rate assessed by investigator, Secondary endpoints included overall response rate (ORR), CR rate, 3-year progression free survival rate, 3-year overall survival rate and safety.


From Jan 2022 to Jun 2023, 27 patients were enrolled with a median age of 58, and 40.7% (11/27) were with IPI ≥3. At the data cut-off date of 30 Jun 2023, all 27 patients received at least one cycle of R-CHOP plus zanubrutinib and included in safety evaluation. Seventeen patients have received 4 cycles treatment and were assessed by CT with CR (n=1) or partial response (n=16); 2 patients withdrew the study before the first assessment. Among the 17 patients, 11 patients completed 6 cycles of treatment and achieved a response (11/11), with a CR (CR and complete metabolic response) of 10/11 (Table). Two patients discontinued after 4 cycles treatment (1 due to outbreak of COVID 19 and 1 due to AE, infectious pneumonia). Ten patients with CR are in the zanubrutinib maintenance treatment, while 1 patient with PR had received salvage therapy decided by the investigator. The most common hematologic TEAEs were neutropenia (33.3% in Grade 1-2, 18.5% in Grade ≥3) and thrombocytopenia (7.4% in Grade 1-2, 11.1% in Grade ≥3), and non-hematologic TEAE includes alanine aminotransferase increased, aspartate aminotransferase increased, rash, hypokalemia, anemia, diarrhea, infectious pneumonia and hemorrhage (Figure). Hypertension and atrial fibrillation/flutter were not observed during the treatment. Four patients experienced SAE of infectious pneumonia (n=1), neutropenia (n=1), and thrombocytopenia (n=2, Grade 3), and were recovered.


At the time of data cut-off 30 Jun 2023, 6 cycles of zanubrutinib combined with R-CHOP regimen was well tolerated and showed a promising response result in untreated non-GCB double-expression DLBCL patients. The study is ongoing and further results will be continuously released.

Disclosures: No relevant conflicts of interest to declare.

*signifies non-member of ASH