Retrospective analysis of orelabrutinib-based chemotherapy-free regimens in Chinese patients with marginal zone lymphoma

Although conventional chemoimmunotherapy remains a mainstay for patients with marginal zone lymphoma (MZL), its toxicities have driven growing interest in chemotherapy-free (chemo-free) alternatives. This real-world study aimed to evaluate the efficacy and safety of orelabrutinib-based chemo-free regimens in Chinese patients with MZL. This retrospective study included 40 patients with histologically confirmed MZL who received orelabrutinib-based chemo-free regimens between July 2022 and November 2025. The assessed outcomes included overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. Of the 40 included patients, 25 (62.5%) received orelabrutinib-based chemo-free regimens as first-line therapy, 15 (37.5%) as second- or later-line therapy. The ORR was 92.5% (95% confidence interval [CI]: 80.1–97.4%), with a complete response rate of 62.5% (95% CI: 45.8–77.3%), and the DCR reached 100.0%. At a median follow-up of 25.2 months (95% CI: 22.4–34.7), median PFS and OS were not reached. The 24-month PFS rate and OS rate were 89.9% and 94.2%, respectively. In subgroup analysis by treatment line, the first-line therapy group achieved an ORR of 100.0% and a DCR of 100.0%, with a 24-month OS rate of 95.5%, while the later-line therapy group showed lower response rates (ORR: 80.0%; DCR: 100.0%) and a 24-month OS rate of 92.3%. Grade ≥ 3 treatment-related adverse events (TRAEs) occurred in 12 patients (30.0%), with thrombocytopenia being the most common; no TRAEs led to treatment discontinuation or death. Orelabrutinib-based chemo-free regimens demonstrate encouraging efficacy and manageable safety in patients with MZL, supporting their potential as a chemo-free treatment option. Further validation in large-scale prospective trials is warranted.