The ZR2-Minichop Study：Zanubrutinib, Lenalidomide, Rituximab, Cyclophosphamide, Vincristine, Epirubicin and Prednisone in Elderly Patients with Previously Untreated Diffuse Large B-Cell Lymphoma

Background: Diffuse large B cell lymphoma (DLBCL) is common in the elderly group. New schedules are required due to the toxicity in classic chemotherapy regimens. Previous studies reported that non-germinal center B cell (non-GCB) subtype aggregates in elderly patients with abnormality in the activated B cell receptor signal and nuclear factor kappa-B pathway. We conducted a prospective trial to investigate the efficacy and safety of the ZR2-miniCHOP schedule (zanubrutinib, lenalidomide, rituximab, cyclophosphamide, vincristine, epirubicin and prednisone) in elder patients newly diagnosed with non-GCB DLBCL.

Methods: This multicenter, single-arm, phase II clinical study started in June 2021 at 6 centers in China. Eligible patients were newly diagnosed non-GCB DLBCL, aged 60 to 80 with Eastern Cooperation Oncology Group (ECOG) performance status over 2, or patients aged over 80 with ECOG status of 0-4. The purpose of this study is to discuss the response, safety and long-term survival with the primary endpoint of objective response rate (ORR) and the secondary endpoint of overall survival (OS) and progression free survival (PFS). Patients would receive 2 cycles induction period with zanubrutinib 160mg twice per day on d1-28, lenalidomide 25mg d1-10 and rituximab 375mg/m² d1, after then combine 4-6 cycles miniCHOP schedule as: cyclophosphamide 400mg/m² d2, vincristine 1.4mg/m² d2, epirubicin 35mg/m² d2 and prednisone 45mg/m² d2-6. Evaluation is conducted after 6 cycles of treatment including the ORR and CR rate by positron emission tomography-computed tomography (PET-CT) and 2-years OS and PFS.

Results: At the data collection duration from June 2021 to June 2022, 26 patients were recruited in this trial. 16 patients were considered for result analysis as 2 withdrawals and 1 drop-out. 7 patients are still in the process of treatment. The median age of the 26 patients enrolled was 77 (range 65-90) years, with 17 patients over 75 years old. The ORR was 93.8% (15/16). The CR rate was 62.5% (10/16). The most common hematology-relevant adverse events (AEs) were neutropenia (7/26) and thrombocytopenia (4/26). Seven AEs over grade 3 occurred during therapy with 3 neutropenia events and 4 thrombocytopenia events. All these patients have administrated the normal dose as the treatment resistance and the toxicity did not affect therapy. One patient died of progressive disease. No treatment-associated death was observed. Generally analyzing, this trial achieved acceptable response and safety.

Conclusion: The ZR2-miniCHOP schedule represented satisfactory efficacy and safety in elderly non-GCB DLBCL.