A phase II study of lenalidomide, zanubrutinib plus obinutuzumab in patients with FLIPI2 high-risk newly diagnosed follicular lymphoma: An interim analysis

Abstract

Abstract Background Follicular lymphoma (FL) is the most common indolent non-Hodgkin lymphoma. Although rituximab plus lenalidomide produces high response rates in newly diagnosed FL, patients with an advanced FLIPI-2 score (3–5) respond less well than those with lower-risk scores. We therefore launched this single-arm, phase II trial to assess the efficacy and safety of obinutuzumab, lenalidomide, and zanubrutinib (ZGR) in treatment-naïve, high-risk (FLIPI2 score 3-5) FL (NCT06549335). Methods Eligible adults (≥18 years) with newly diagnosed grade 1–3a FL and FLIPI-2 scores 3–5 received six 28-day induction cycles: obinutuzumab 1,000 mg intravenously on days 1, 8, and 15 of cycle 1 and day 1 of cycles 2–6; lenalidomide 25 mg orally days 2–11; and zanubrutinib 160 mg orally twice daily continuously. Maintenance consisted of obinutuzumab every 3 months for 2 years and lenalidomide 25 mg days 1–10 monthly for six cycles. The primary endpoint was overall response rate (ORR) after induction; secondary endpoints included complete response (CR) rate, duration of response (DOR), 2-year progression-free survival (PFS), and 2-year overall survival (OS). Results As of 1 June 2025, 30 patients had been enrolled (median age 57 years, range 28–78). All presented with advanced Ann Arbor stage; 43 % had elevated LDH, and 57 % had multiple extranodal sites. Among 28 response-evaluable patients, ORR was 89.3 % (25/28) and CR rate was 67.8 % (19/28). No treatment discontinuations have occurred for safety reasons. Conclusion The findings here provides clinical evidence on the efficacy of the ZGR regimen in de novo high-risk FL patients. We will further explore the potential therapeutic mechanism of this treatment combination.