Efficacy and safety of zanubrutinib combination therapy and monotherapy maintenance in patients with follicular lymphoma: A retrospective single-center analysis

Abstract Background Zanubrutinib, a next-generation Bruton's tyrosine kinase inhibitor, has shown promise in the management of indolent B-cell lymphomas. However, real-world data on its efficacy and safety, particularly as combination therapy or maintenance treatment in follicular lymphoma (FL), remain limited. Methods We retrospectively analyzed the records of 15 patients with FL treated at Fujian Medical University Union Hospital between May 2023 and July 2025, among which 8 patients received 6–8 cycles of zanubrutinib in combination with rituximab or obinutuzumab, while 7 patients underwent zanubrutinib monotherapy for maintenance after achieving complete response (CR) from previous first-line regimens without zanubrutinib. Baseline characteristics, treatment history, and responses were collected. Efficacy was evaluated according to the Lugano 2014 criteria, with CR rate and overall response rate (ORR) as primary endpoints. Results Among the eight patients receiving zanubrutinib in combination with immunotherapy, five (62.5%) had grade 2 FL and three (37.5%) had grade 3 disease. The median age was 49 years (range, 35–65), with two males (25%) and six females (75%). All patients presented with Ann Arbor stage III–IV disease, and five (62.5%) had bone marrow involvement. Two patients (25%) had FLIPI scores of 3–5, and two (25%) had FLIPI-2 scores of 3–5. The median follow-up duration was 7 months (range, 6–14). The ORR was 87.5%, with a CR rate of 37.5%. Median progression-free survival (PFS) and overall survival (OS) were not reached during the observation period. In the maintenance monotherapy group, seven patients received zanubrutinib as maintenance following complete remission induced by non-zanubrutinib first-line therapy. Of these, one (14.3%) had grade 1 FL, four (57.1%) had grade 2, and two (28.6%) had grade 3 disease. The median age was 61 years (range, 48–68), with three males (42.9%) and four females (57.1%). Six patients (85.7%) were at Ann Arbor stage III–IV, and four (57.1%) had bone marrow involvement. FLIPI scores of 3–5 were observed in four (57.1%), and FLIPI-2 scores of 3–5 in two (28.6%) patients. The median follow-up duration was 6 months. As of July 2025, no recurrences had been observed in this group. Conclusions In this real-world cohort, zanubrutinib, administered either in combination with immunotherapy or as maintenance monotherapy, demonstrated favorable efficacy and a manageable safety profile in patients with FL. These results support further investigation of zanubrutinib-based regimens in this patient population.