The chemotherapy-free combination of obinutuzumab (Gazyva) and zanubrutinib (Brukinsa) elicited a complete response (CR) rate of 80% as first-line treatment for older patients with mantle cell lymphoma (MCL), according to data from a phase 2 trial (ChiCTR2300071433) presented in a poster session at the
Among evaluable patients assessed by PET-CT (n = 45), 80% achieved a CR, and 5 patients (11.1%) experienced a partial response, translating to an overall response rate (ORR) of 91.1%. At a median follow-up of 12 months, the median progression-free survival (PFS) and overall survival (OS) had not been reached. One patient died due to disease progression, and 1 patient died due to COVID-19.
“The combination of obinutuzumab and zanubrutinib demonstrated promising efficacy and a manageable safety profile in [older] patients with previously untreated MCL, supporting a chemo-free therapeutic approach in this population,” lead study author Yanan Zhu, MD, of the First Affiliated Hospital of Zhejiang University School of Medicine in Hangzhou, China, and colleagues wrote in a poster presentation of the data.
The open-label, multicenter, single-arm phase 2 trial enrolled patients at least 65 years of age with newly diagnosed MCL.
Induction therapy consisted of obinutuzumab at 1000 mg administered intravenously on days 1, 8, and 15 of the first 28-day cycle and on day 1 of cycles 2 through 4, in combination with oral zanubrutinib at 160 mg twice daily beginning in cycle 2. Patients who achieved a CR after induction proceeded to zanubrutinib maintenance, whereas those with a partial response received 2 additional cycles of obinutuzumab plus zanubrutinib before transitioning to zanubrutinib maintenance.
CR rate served as the primary end point. Secondary end points included ORR, PFS, OS, and safety. Earlier data from the trial, based on the first 10 patients enrolled, were presented at the 2024 EHA Congress.2
A total of 49 patients were enrolled, and they had a median age of 73 years.1 Bone marrow involvement was present in 34 patients (69.4%), 14 patients (28.6%) were classified as high risk according to the simplified MCL International Prognostic Index, and 23 patients had a Ki-67 index of at least 30%. One patient (2.0%) had a prior history of atrial fibrillation. Next-generation sequencing was performed in 32 patients and identified TP53 mutations in 7 patients (22%).
Most adverse effects (AEs) were grade 1 or 2. Three patients experienced grade 2 infusion-related reactions during the first obinutuzumab infusion, and 6 patients developed grade 3 or 4 thrombocytopenia during the first obinutuzumab cycle. One patient developed new-onset paroxysmal atrial fibrillation, and 1 patient experienced grade 1 gastrointestinal bleeding.
