Bispecific Antibody Therapy Achieves Sustained Remissions in Follicular Lymphoma
Mosunetuzumab, a CD20xCD3 T-cell-engaging bispecific antibody, has shown durable efficacy in relapsed or refractory (R/R) follicular lymphoma (FL) after 2 or more prior lines of therapy. In a phase 1/2 study, published in Blood, with a median follow-up of 37.4 months, the complete response (CR) rate was 60%, and the overall response rate (ORR) was 77.8%. Among the 54 patients who achieved CR, 49 remained in remission at the end of treatment, with the median duration of CR not reached. The estimated 30-month remission rate was 72.4%, and the 36-month overall survival (OS) rate was 82.4%. Median progression-free survival (PFS) was 24.0 months. No new cytokine release syndrome (CRS) events or serious adverse events were reported, supporting mosunetuzumab as a safe, fixed-duration outpatient therapy.
FL is an indolent but relapsing lymphoma that often becomes refractory to treatment. While novel therapies have improved outcomes, late-line options remain limited. Mosunetuzumab redirects T cells to eliminate malignant B cells and has received regulatory approvals based on promising early data. This study confirms its long-term benefit, with most complete responders maintaining remission for years. The treatment was effective even in heavily pretreated patients, with some successfully retreated upon relapse. CD19+ B-cell recovery occurred at a median of 18.4 months, supporting the feasibility of fixed-duration treatment.
Compared with prior therapies, mosunetuzumab demonstrated higher response rates and longer remissions. It outperformed patients’ last prior treatment in CR rate (60% vs 35.6%) and median PFS (24.0 vs 12.1 months). Unlike continuous or chimeric antigen receptor (CAR) T-cell therapies, mosunetuzumab offers a convenient, off-the-shelf alternative with a finite treatment course. With 3 years of follow-up, this study provides the longest reported data on bispecific antibody therapy in R/R FL, reinforcing mosunetuzumab as a highly effective and safe treatment option.
“Results confirm and extend findings of the primary analysis results, providing further evidence of clinically meaningful and sustained benefit of mosunetuzumab, with a manageable safety profile,” researchers concluded “B-cell counts progressively recovered to normal levels after fixed-duration mosunetuzumab therapy and evidence of potential benefit from retreatment was demonstrated.”
Reference
Sehn LH, Bartlett NL, Matasar MJ, et al. Long-term 3-year follow-up of mosunetuzumab in relapsed or refractory follicular lymphoma after ≥2 prior therapies. Blood. 2025;145(7):708-719. doi:10.1182/blood.2024025454
