Zanubrutinib Plus R-CHOP (ZR-CHOP) in Non-Germinal Center B-Cell-like Diffuse Large B-Cell Lymphoma Patients Who Were Positron Emission Tomography-Positive after Two Cycles of R-CHOP: A Single-Arm, Open-Label, Multicenter Prospective Study

作者：Jie Wang, He Li, Chenlu Yang, Di Wu, Xingli Zou, Tao Yang, Liangliang Ma, Fang Xu, Jie Wang, Minggang Su, Sha Zhao, Ji Lin, Yao Liu, Pengcheng He, Ting Niu · 发表于：Blood · 年份：2024 · DOI：10.1182/blood-2024-193927 · 研究领域：Chronic Lymphocytic Leukemia Research、Lymphoma Diagnosis and Treatment、Chronic Myeloid Leukemia Treatments

Background: R-CHOP is a standard treatment for previously untreated diffuse large B-cell lymphoma (DLBCL), however, more than one-third of patients are not cured by R-CHOP. There is a clear need to improve the prognosis of patients, especially for those with factors associated with poor prognosis, such as non-germinal center B-cell-like (non-GCB) subtype and positive interim positron emission tomography (PET). Bruton's tyrosine kinase inhibitors (BTKi) have established therapeutic activity in B-cell malignancies, with modest activity in DLBCL. Zanubrutinib, a potent and selective BTKi, was evaluated in patients with relapsed or refractory (R/R) non-GCB DLBCL. Zanubrutinib showed minimized off-target activities against interleukin-2-inducible T cell kinase (ITK) and reduced interference of ITK-mediated, rituximab-induced, antibody-dependent cellular cytotoxicity. Therefore, ZR-CHOP is a potentially effective regimen. Aim: We designed a treatment escalation regimen with ZR-CHOP, followed by zanubrutinib maintenance, for non-GCB DLBCL patients who were PET positive after two cycles of R-CHOP (ChiCTR2100054552). Here, we report the preliminary results from this ongoing perspective trial. Methods: Patients with non-GCB DLBCL who were PET positive (Deauville scores 4 or 5) after two cycles of R-CHOP were enrolled. Patients with PET negative or PD were excluded. Patients received ZR-CHOP in a 21-day cycle for 6 cycles (induction), followed by zanubrutinib monotherapy as maintenance ...