Abstract IntroductionObinutuzumab combined with immunochemotherapy significantly improves outcomes in follicular lymphoma (FL) with high tumor burden. Although the G-CHOP regimen demonstrates an advantage in prolonging progression-free survival (PFS) compared to G-CVP, its clinical application is limited by anthracycline-associated hematologic toxicity and cardiotoxicity. Additionally, the GB regimen increases infection risk and impairs T-cell function. Based on the promising results of the ROSEWOOD trial, zanubrutinib combined with obinutuzumab was approved in China (May 2024) for relapsed/refractory FL. This study aims to evaluate the efficacy and safety of zanubrutinib plus G-CVP (ZG-CVP) as first-line therapy for FL, to provide more therapeutic options featuring both high response rates and low toxicity. MethodsThis study retrospectively analyzed the clinical data of previously untreated FL patients who received the ZG-CVP regimen between July 2024 and June 2025. The eligibility criteria were as follows: age ≥ 18 years; grade 1-3a; stage III/IV or stage II with bulky tumors (maximum tumor diameter ≥ 7 cm); receiving at least 2 cycles of ZG-CVP; meeting the GELF high tumor burden criteria. FL patients received six 21-day cycles of ZG-CVP: Zanubrutinib: 160 mg orally twice daily on days 1-21; Cyclophosphamide: 750 mg/m² IV on day 1; Vindesine: 3 mg/m² (maximum 4 mg) IV on day 1; Prednisone: 30 mg orally three times daily on days 1-5; Obinutuzumab: cycle 1: 1000 mg IV on days 1, 8, and 15; cycles 2-6: 1000 mg IV on day 1. Advanced-stage patients who achieved complete response (CR) or partial response (PR) received maintenance treatment with obinutuzumab 1000 mg intravenously every two months for two years, while stage II patients did not. Efficacy was assessed by complete response rate (CRR) and objective response rate (ORR), with safety assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) (version 5.0). ResultsA total of 23 patients were included in the analysis. The median age was 56 years (range: 37-75 years), and 52.2% were male. Histopathologically, 65.2% were classified as grade 1-2 FL with 34.8% having grade 3a disease. At diagnosis, 95.7% were Ann Arbor stage III-IV; 8.7% presented with B symptoms, and 17.4% had bulky tumors. Bone marrow involvement and extranodal involvement were observed in 47.8% and 56.5% of patients, respectively. According to the FLIPI, 13.1% of patients were classified as low-risk (0-1 points), 65.2% as intermediate-risk (2 points), and 21.7% as high-risk (≥3 points), while by FLIPI-2 criteria, 60.9% were low-risk (0-1 points), 21.7% were intermediate-risk (2 points), and 17.4% were high-risk (≥3 points).During a median follow-up of 6.0 months (range: 0.7-11.2 months), 78.3% (18/23) of the patients completed all 6 treatment cycles, with 1 completing 5 cycles, 3 completing 4 cycles, and 1 discontinuing treatment after 2 cycles due to severe pneumonia. After 2 cycles, all 23 patients achieved PR. Following 4 cycles, 21 patients underwent interim assessment, demonstrating a CRR of 95.2% and an ORR of 100%. Of the 18 patients completed 6 cycles, all 16 evaluable patients achieved CR (100%), including the one who previously achieved only PR after 4 cycles. All advanced-stage patients proceeded to maintenance therapy.The most common adverse events of any grade were anemia (56.5%, 13/23), neutropenia (47.8%, 11/23) and thrombocytopenia (47.8%, 11/23) .The vast majority of AEs were grade 1-2 and did not cause treatment discontinuation. Notably, unlike the G-CHOP regimen, the ZG-CVP regimen does not require central venous catheter placement, thereby reducing the risk of catheter-associated thrombosis. ConclusionThis retrospective study demonstrates that the combination of zanubrutinib with G-CVP was highly effective and well-tolerated in previously untreated FL. Based on these findings, we plan to conduct a phase II, single-arm, multicenter clinical trial (NCT06918015) to further evaluate the efficacy and safety of ZG-CVP as first-line therapy for FL.
Xu et al. (Mon,) studied this question.