CAR T-Cell Therapy Offers Superior Efficacy Over Bispecific Antibodies for R/R Follicular Lymphoma but With Higher Toxicity, Meta-Analysis Finds

Chimeric antigen receptor (CAR) T-cell therapy was associated with significantly higher response rates and superior responses compared to bispecific antibodies (BsAb) for the treatment of relapsed/refractory (R/R) follicular lymphoma (FL), though with an increased incidence of neurotoxicity, according to systematic review and meta-analysis  results published in Frontiers in Immunology.

“Although both CAR-T therapy and BsAb have shown significant potential in the treatment of R/R FL,” the study authors explained, “the lack of direct head-to-head studies comparing the efficacy, incidence of serious adverse events, and prognosis of patients between the 2 poses a challenge for clinical decision-making.”

Follicular lymphoma is often recurring or refractory, and disease progression within 24 months of first-line treatment indicates shorter overall survival (OS), highlighting a need for improved therapeutic strategies for these patients. To address this, researchers conducted a meta-analysis of 12 studies to determine the efficacy of CAR T-cell therapy products compared with bispecific antibodies for the treatment of R/R FL. 

At analysis, 12 studies were included, of which 6 investigated CAR T-cell therapies and 6 investigated bispecific antibodies. In the 6 included CAR-T studies, treatments evaluated were axicabtagene ciloleucel (n= 1), tisagenlecleucel (n= 1), lisocabtagene maraleucel (n= 1), CTL019 (n= 1), and CD19 CAR T-cell groups (n= 2). The 6 included bispecific antibody studies evaluated mosunetuzumab (n= 1), epcoritamab (n= 1), odronextamab (n= 2), and glofitamab (n= 2). 

The pooled overall response rate (ORR) was 92% (95% CO, 0.87 to 0.97) for patients treated with any CAR T-cell therapy versus 77% (95% CI, 0.68 to 0.86; P = 0.01) for any bispecific antibody. Additionally, the complete remission (CR) rate was 82% (95% CI, 0.72 to 0.91) for CAR-T therapy compared with 65% (95% CI, 0.58 to 0.72; P < 0.001). One-year PFS was 75% (95% CI< 0.66 to 0.83) among patients treated with CAR-T therapies and 61% (95% CI, 0.52 to 0.70; P = 0.03) among patients treated with bispecific antibodies.

Among both the CAR-T group and the bispecific antibody group, the incidence of grade 2 or higher cytokine release syndrome (CRS) was 0.03 (95% CI, 0.00 to 0.07 and 95% CI, 0.02 to 0.04, respectively). Grade 3 or higher neurologic events were higher in the CAR-T group (0.07; 95% CI, 0.02 to 0.13) compared with the bispecific antibody group (0.00; 95% CI, 0.00 to 0.01; P = 0.02). In addition, the bispecific antibody group had higher rates of grade 3 or higher infections than the CAR-T group (0.18; 95% CI, 0.13 to 0.23 vs 0.09; 95% CI, 0.02 to 0.17, P = 0.07).

The researchers concluded, “this pooled analysis showed that CAR T-cell therapy demonstrated a higher CR, ORR and one-year PFS in third or subsequent lines of treatment compared to BsAb therapy, but was accompanied by an increased incidence of severe neurotoxicity.”

Source:

He Y, Qiu L, Chen D, et al. CAR T-cells vs. bispecific antibodies as third- or later-line treatment for relapsed/refractory follicular lymphoma: a literature review and meta-analysis. Frontiers in Immunology. Published online September 28, 2025. doi:10.3389/fimmu.2025.1611984