The Efficacy and Safety of Obinutuzumab with Zanubrutinib As First-Line Treatment in Older Patients with Mantle Cell Lymphoma

Backgroud: Mantle cell lymphoma (MCL) is a heterogeneous malignancy and its incidence increases with age. Elder patients have poor performance status and low tolerance to chemotherapy, so many investigators look for chemo-free therapeutic approaches for newly diagnosed elderly MCL patients.

Aims: This study aims to investigate the efficacy and safety of a combination of obinutuzumab plus zanubrutinib (GZ) in previously untreated elderly patients with MCL.

Methods: Elderly patients (age ≥ 65 years) with newly diagnosed MCL were enrolled in this open-label, multicenter, single-arm, phase II clinical trial (ChiCTR2300071433), blastoid or pleomorphic histology were excluded. Patients received obinutuzumab (1000mg, intravenously, on days 1, 8, and 15 of cycle 1 and day 1 of cycle 2-4, 4 weeks per cycle), and zanubrutinib (160 mg twice daily, orally, from cycle 2) as induction therapy. Patients achieved complete remission (CR) were followed by zanubrutinib maintenance. Patients achieved partial remission (PR) received obinutuzumab for another 2 cycles and then zanubrutinib maintenance. Zanubrutinib was administered until disease progression or unacceptable toxicity or any other reasons of discontinuation. The primary endpoint was complete response rate (CRR). The secondary endpoints were overall response rate (ORR), overall survival (OS), progression free survival (PFS) and safety profiles.

Results: 19 patients were enrolled with a median age of 72 years. 14 patients had bone marrow involvement. High mantle cell lymphoma international prognostic index (MIPI) risk score was observed in 7 patients, and 10 patients had ki-67≥30%. 1 patient had a history of atrial fibrillation. Next-generation sequencing results were available in 15 patients, and detected 4 (26.7%) TP53 mutation. 9 patients had finished induction therapy, with 8 (88.9%) achieved CR, 1 achieved PR, and the ORR was 100%. With a median follow-up of 7 months, no patients had disease progression.

Most adverse events (AEs) were grade 1-2. 2 patients had grade 2 infusion-related response during the first obinutuzumab dose, each developed grade 3 or grade 4 thrombocytopenia, and both recovered in a week. 1 patient had grade 3 anemia, 1 patient had Covid-19 infection along with paroxysmal atrial fibrillation. No bleeding was observed. No patient discontinued therapy.

Conclusion: Obinutuzumab plus zanubrutinib demonstrated a favorable efficacy and a manageable safety profile in elderly patients with untreated MCL.