815MO - A prospective study of orelabrutinib plus obinutuzumab (O2) in treatment-naïve marginal zone lymphoma (MZL): Preliminary analysis on efficacy and safety

Background

There is no well-established standard first-line treatment for symptomatic MZL patients (pts). Orelabrutinib (ORE) was the first approved BTK inhibitor in China for relapsed or refractory MZL treatment. However, evidence supporting ORE as a first-line therapy for MZL is lacking. This prospective study evaluated a chemotherapy-free regimen of ORE plus anti-CD20 antibody obinutuzumab (OBI) in treatment-naïve MZL.

Methods

This study enrolled pts with confirmed CD20-positive MZL, who has progressed/relapsed after or were ineligible for local therapy. Pts received induction therapy with ORE (orally 150 mg/day) plus OBI (intravenously 1000 mg; cycle 1: day 1, 8, 15; cycle 2-6: day 1) for 6 cycles every 4 weeks, and responders maintained with ORE for 1 year.

Results

Nineteen pts with MZL (17 EMZL, 1 SMZL, 1 unknown) were enrolled in this study from 13 Jun. 2023 to 11 Apr. 2024. Pts characteristics included a median age of 60 years (range 25-77), 78.9% Ann Arbor stage II-IV disease, 73.7% intermediate and high-risk MZL-IPI scores and 31.6% prior local therapy. At a median follow-up of 5.4 months,14 pts had ≥1 efficacy assessment, the median time to response was 3.1 months and the best objective response rate (ORR) was 100% (57.1% complete response rate [CRR]). Of 13 pts evaluable for response at the end of cycle 3, ORR was 100%. Nine (69.2%) pts have completed the 6-cycle induction therapy and received ORE maintenance. At the end of cycle 6, 9 pts had an ORR of 100%, with a CRR of 55.6% (Table). Eighteen pts had completed ≥1 cycle of therapy and were analyzed for safety. Adverse events included: neutropenia (grade [G] 1, n=1; G4, n=1), thrombocytopenia (G2, n=1), transaminase increased (G1, n=2), and leukopenia (G1, n=1). Table: 815MO

Response during O2 treatment

Conclusions

Our preliminary data demonstrated that the O2 regimen was promising in treatment-naïve MZL. Trial recruitment is still ongoing. More updated data will be presented in future.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Zhongshan Hospital Fudan University.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.