Efficacy and safety of subcutaneous mosunetuzumab in combination with lenalidomide and as a monotherapy in Japanese patients with relapsed/refractory follicular lymphoma

Abstract Background JO40295 (jRCT2080223801) evaluated the efficacy and safety of subcutaneous (SC) mosunetuzumab, in combination with lenalidomide and as monotherapy, in Japanese patients with relapsed/refractory (R/R) follicular lymphoma (FL). We report outcomes from the interim analysis of the FLMOON-2 (≥ 1 prior therapy; mosunetuzumab plus lenalidomide) and primary analysis of the FLMOON-3 (≥ 2 prior therapies; mosunetuzumab monotherapy) cohorts. Methods Mosunetuzumab SC was administered with Cycle (C)1 step-up dosing in both cohorts: C1 Day (D)1, 5 mg; C1D8, D15 and C2 onwards, 45 mg. In FLMOON-2, oral lenalidomide was administered from C2 onwards, on D1–21 of each cycle. Treatment was administered up to C12 in FLMOON-2 and C8 or C17 in FLMOON-3. The primary endpoint was independent review facility-assessed complete response (CR) rate. Results At the clinical cut-off date (FLMOON-2: April 4, 2024; FLMOON-3: March 4, 2024), in the efficacy-evaluable populations, CR rate was 92.3% in FLMOON-2 (n = 13) and 100% in FLMOON-3 (n = 5). In the safety-evaluable populations (FLMOON-2, n = 17; FLMOON-3, n = 5), Grade 3/4 adverse events (AEs) occurred in 64.7% of patients in FLMOON-2 and 20.0% in FLMOON-3. No Grade 5 AEs or AEs leading to treatment discontinuation occurred in either cohort. Cytokine release syndrome was reported in 47.1% of patients in FLMOON-2 and 20.0% in FLMOON-3. Serum mosunetuzumab concentration peaked with the third dose of mosunetuzumab in C1 and reached a steady state with repeated dosing. Conclusion Mosunetuzumab SC, in combination with lenalidomide and as monotherapy, demonstrated promising efficacy with a manageable safety profile in Japanese patients with R/R FL.