CD3/CD20 Bispecific T-cell Engagers Show High Response Rates in Follicular Lymphoma
Key Clinical Summary
- Bispecific CD3/CD20 T-cell engagers (TCEs) show high efficacy in follicular lymphoma, with pooled frontline overall response rate (ORR) 93% and complete response rate (CR) 81%, and strong activity in relapsed or refractory disease (ORR 81%, CR 67%) across 14 early-phase trials (n = 911).
- Combination regimens may enhance responses, with some studies reporting ORR up to 96% and CR 87%, suggesting potential benefit over monotherapy.
- Toxicities were manageable: cytokine release syndrome (CRS) was common (~60%) but rarely severe (1.9% grade ≥3), and immune effector cell-associated neurotoxicity syndrome (ICANS) was infrequent (3.1%), supporting continued development and earlier-line evaluation.
Bispecific CD3/CD20 T-cell engager therapies are demonstrating high response rates and manageable toxicity in follicular lymphoma, supporting continued development and evaluation in earlier lines of treatment, according to study results published in Blood.
Follicular lymphoma is the most common indolent non-Hodgkin lymphoma and usually progresses slowly but is characterized by repeated relapses and eventual resistance to standard treatments. Recently, bispecific CD3/CD20 TCEs have emerged as a promising therapy by redirecting T cells to target malignant B cells.
Researchers systematically reviewed published phase 1 and 2 trials of TCE therapies used as monotherapy or in combination regimens. Because phase 3 results are not yet available, the analysis focused on early-phase data. Using a random-effects single-arm pooled meta-analysis, investigators combined ORR and CR rates across studies. Studies were grouped into 2 cohorts: previously untreated frontline follicular lymphoma and relapsed or refractory disease.
A total of 14 trials involving 911 patients met the inclusion criteria. In the frontline setting, pooled results showed an ORR of 93% (95% CI, 89-95%) and a CR rate of 81% (95% CI, 72-86%). Combination regimens produced particularly strong outcomes with ORR 93% (95% CI, 87-97%) and CR 86% (95% CI, 79-91%), while monotherapy trials demonstrated ORR 92% (95% CI, 86-96%) and CR 75% (95% CI, 62-84%). In the relapsed or refractory setting, pooled monotherapy results showed an ORR of 81% (95% CI, 77-84%) and a CR rate of 67% (95% CI, 61-72%). Subgroup analysis found ORR 87% for epcoritamab and 79% for mosunetuzumab. Notably, a single trial evaluating epcoritamab combined with lenalidomide and rituximab (R2) reported an ORR of 96% and a CR rate of 87%.
Safety outcomes reflected expected immune-related toxicities. Across all trials, the CRS rate of any grade was 60.7%, which decreased to 55.1% after excluding one outlier study. However, grade ≥3 CRS occurred in only 1.9% of patients, indicating most cases were mild and manageable. ICANS was uncommon, occurring in 3.1% of patients, with only one reported case of grade 3 ICANS.
“These findings underscore the huge potential and relative similarity in efficacy in terms of ORR and CR rates that these agents have supporting the continuation of phase III trials and earlier lines of use,” concluded the study authors.
Reference
Fahmawi S, Lutfi F, Ahmad J, Suleman N. Pooled analysis of early-phase trials highlights robust activity of CD3-CD20 T-cell engagers in follicular lymphoma. Blood. 2025;146(suppl 1):5387. doi:10.1182/blood-2025-5387
