Obinutuzumab With Zanubrutinib May Be a Chemo-Free Option for Elderly Patients With MCL

Obinutuzumab in combination with zanubrutinib showed favorable efficacy and manageable safety in elderly patients with untreated mantle cell lymphoma (MCL), according to findings from a phase 2 study presented in a poster during the 66^th American Society of Hematology Annual Meeting & Exposition.

The study enrolled 19 Chinese patients with untreated MCL who were 65 years or older. The median age of the study population was 72 years. Fourteen of the patients enrolled had bone marrow involvement. Seven of the patients in the study had high MCL international prognostic index (MIPI) risk score, and 10 patients had ki-67≥30%. One patient had a history of atrial fibrillation (AFib). Fifteen patients had next-generation sequencing (NGS) results; of those sequenced, four patients (26.7%) had TP53-mutated disease.

As induction therapy, obinutuzumab was administered intravenously at 1000 mg on days 1, 8, and 15 of cycle 1 and day 1 of cycles 2-4. Zanubrutinib was administered orally at 160 mg twice daily, beginning during cycle 2. In the event of a complete response (CR), patients were given zanubrutinib maintenance. Those who achieved a partial response (PR) were given another two cycles of obinutuzumab plus zanubrutinib as maintenance therapy.

Overall, nine patients completed induction therapy. The CR rate observed was 88.9%, and the PR rate was 11.1% for an objective response rate (ORR) of 100%. At a median follow-up of seven months, no disease progression was observed among patients in the study.

Most of the adverse events (AEs) seen among patients were grades 1 or 2. There were two cases of grade 2 infusion-related responses after obinutuzumab was administered, and each patient also developed grade 3 or 4 thrombocytopenia. Recovery from thrombocytopenia occurred within a week, investigators noted. Grade 3 anemia occurred in one patient. Another patient experienced COVID-19 infection and paroxysmal AFib. There were no occurrences of bleeding, and no patients discontinued treatment.

REFERENCE

Zhu Y, Lv Y, Ye X, et al. The efficacy and safety of obinutuzumab with zanubrutinib as first-line treatment in older patients with mantle cell lymphoma. Presented at: 66^th American Society of Hematology Annual Meeting; December 7-10, 2024; San Diego, CA. Abstract 1630.