Systematic review and meta-analysis: CAR-T vs bispecific antibody as third or later-line therapy for follicular lymphoma.

There is currently no clear consensus on the standard of care for relapsed or refractory follicular lymphoma (FL) beyond third-line therapy, where both anti-CD19 CAR-T-cell therapy (CAR-T) and CD3×CD20 bispecific antibodies (BsAbs) have demonstrated efficacy. This study aimed to examine their efficacy and toxicity profiles. Relevant studies published between January 2010 and June 2025 were identified through major databases. Of 3960 records screened, 12 studies met the inclusion criteria-7 involving CAR-T and 5 involving BsAbs. The pooled overall response rate (ORR) and complete response rate (CRR) were 93% and 82% for CAR-T, compared with 82% and 67% for BsAbs (p = 0.0002 and p = 0.005, respectively). Among patients with POD24, the CRR was 75% for CAR-T and 69% for BsAbs (p = 0.56). This translated into improved progression-free survival (PFS) with CAR-T: 6-month, 1-year and 3-year PFS rates were 85%, 74% and 54%, respectively, compared with 74%, 62%, and 42% for BsAbs (p = 0.006, p = 0.002 and p = 0.009, respectively). A trend toward higher 3-year overall survival (OS) was observed with CAR-T (80%) versus BsAbs (73%) (p = 0.48). Grade ≥3 immune effector cell-associated neurotoxicity syndrome (ICANS) occurred more frequently with CAR-T (8% vs. 0%, p = 0.04), whereas grade ≥3 infections were numerically higher with BsAbs (17% vs. 9%, p = 0.31). One-year non-relapse mortality (NRM) was similar between groups at 3%. Overall, CAR-T demonstrated potentially higher efficacy in this non-comparative meta-analysis, while the two therapies exhibited noticeable differences in toxicity profiles.