Promising new combination therapy for FL

The combination of mosunetuzumab and zanubrutinib was associated with profound anti-tumour activity in patients with previously untreated, high-burden follicular lymphoma (FL). The treatment regimen was well-tolerated, making it a promising new option for this patient population.

Mosunetuzumab is an immunoglobulin G1 (IgG1)-like CD3xCD20 bispecific antibody, and zanubrutinib is a second-generation Bruton’s tyrosine-kinase (BTK) inhibitor. The combination was assessed in a phase 2 study that included 54 participants with previously untreated CD20+ FL who required therapy per the Groupe d’Étude des Lymphomes Folliculaires (GELF) criteria. “The GELF criteria define a high tumour burden in patients with FL,” clarified Dr Lorenzo Falchi (Memorial Sloan Kettering Cancer Center, NY, USA) [1]. The primary endpoint was complete response per the Lugano criteria.

After a median follow-up of 6.5 months, the overall response rate was 92%, and the complete response rate was 82%. “Best responses were generally achieved early, around 3 months of follow-up,” added Dr Falchi. He further mentioned that no new safety issues were observed for the study agents. The most common adverse events were injection-site reactions (67%), cytokine release syndrome (CRS; 61%), dry skin (58%), and infections (39%). “Almost all adverse events were of grade 1 or 2,” said Dr Falchi. For CRS specifically, 52% of participants had experienced grade 1 events, and 9% had experienced grade 2 events. The observed infections were mostly mild, and hospitalisation was rarely required (3%).

In conclusion, the combination of mosunetuzumab and zanubrutinib demonstrated encouraging efficacy and safety data among patients with newly diagnosed, high-burden FL in this phase 2 study. A longer follow-up will be needed to assess the durability of the response.

1. Falchi L, et al. Combined mosunetuzumab and zanubrutinib for the treatment of patients with newly diagnosed high-burden follicular lymphoma: first results of the multicenter phase 2 MITHIC-FL2 trial. Abstract 463, American Society of Hematology (ASH) annual meeting 2025, 6–9 December, Orlando, Florida, USA.

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Posted on 22 December 2025