MITHIC-FL2 phase II: Mosunetuzumab + zanubrutinib in ND FL

First results from the phase II MITHIC-FL2 trial, investigating mosunetuzumab + zanubrutinib in 57 adult patients with previously untreated, newly diagnosed (ND), high-burden follicular lymphoma (FL), were presented by Lorenzo Falchi at the 67th American Society of Hematology (ASH) Annual Meeting and Exposition, December 6–9, 2025, Orlando, US. The primary endpoint was complete response (CR) rate at the end of study therapy. Of 57 patients that signed informed consent, 54 and 51 were evaluable for safety and efficacy analyses, respectively. 

Key data: At median follow-up of 6.5 months, overall response rate (ORR) was 92% and CR rate was 82%, with 10% of patients achieving a partial response (PR). Stable and progressive disease were reported in 2% and 6% of patients, respectively. Response dynamics showed that the best responses were generally achieved early, at the 3-month timepoint. Dual therapy receivers also exhibited marked tumor burden reduction, with all except two patients achieving ≥50% tumor volume reduction from baseline. The safety profile was favorable, with mostly Grade 1–2 adverse events (AEs) and no AE-related treatment discontinuations. The predominant AEs were injection site reaction (67%), cytokine release syndrome (CRS) (61%), and dry skin (58%); all Grade 1/2.

Key learning: Mosunetuzumab + zanubrutinib exhibited clinically significant efficacy and a favorable safety profile in patients with previously untreated, ND, high-burden FL, supporting the continued evaluation of this combination in this patient population.