Real-world outcomes of bispecific antibodies in relapsed/refractory (R/R) follicular lymphoma (FL).

Abstract

7010 Background: Mosunetuzumab (mosun) and epcoritamab (epco) are bispecific antibodies (BsAbs) approved for R/R FL, with pivotal trials (n=90-128) initially demonstrating 60-63% complete response rate (CRR), 80-82% overall response rate (ORR), and 1-year progression-free survival (PFS) rate of 58-66%. Real-world outcomes remain limited. We report the real-world efficacy and safety outcomes of BsAbs for patients (pts) with R/R FL treated in the Collaborative United States Bispecifics Consortium (CUBIC). Methods: This is a multicenter retrospective study of adult pts with R/R FL treated with standard of care mosun or epco between 2/2023 and 9/2025 at eight CUBIC centers. Efficacy outcomes included ORR, CRR, PFS, and overall survival (OS). PFS and OS were estimated using the Kaplan-Meier method. Safety outcomes included incidence and grade (G) of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Results: A total of 99 pts with R/R FL were treated with BsAb, with 92% receiving mosun (n=91) and 8% (n=8) receiving epco. Median age was 68 years (range 33-101), 61% were ≥65 years (n=60), 63% were male (n=62), 8% Hispanic (n=8), 92% (n=79) had ECOG performance status (PS) of 0-1, 51% (n=42) had FLIPI ≥3, and 31% (n=30) had elevated LDH. Median prior lines of therapy were 3 (range 1-14), and 15% (n=15) had prior CAR-T. Among 96 pts with complete response data, the ORR was 87% and CRR was 72%. Median time to best response was 2.9 months (mo) (range 1.2-12.7). Response rates were not significantly associated with BsAb, ECOG PS, FLIPI, elevated LDH, or prior CAR-T. At median follow-up of 16.9 mo, the one-yr and 18 mo PFS rates were 72% (95%CI 62-83%) and 56% (95%CI 45-70%). One-yr and 18 mo OS rates were 94% (95%CI 90-99%) and 92% (95%CI 86-99%), respectively. Hispanic pts had better PFS than non-Hispanic pts (2-yr PFS 100% vs 42%, p=0.02). PFS was not significantly influenced by BsAb product, elevated LDH, ECOG PS, FLIPI, or prior CAR-T. Patients with ECOG of 2 had inferior OS than pts with ECOG of 0-1 (2-yr OS 43% vs 89%, p=0.02). Male sex was associated with inferior OS compared to female sex (2-yr OS 76% vs 100%, p=0.02). No differences in ORR, CRR, PFS, or OS were observed between pts <65 vs ≥65 yrs or <80 vs ≥80 yrs. Of 96 pts with complete safety data, CRS occurred in 34% of pts (G1 26%; G2 6%), with no ≥G3 events. ICANS occurred in 3% of pts (n=3), all G1 events. The incidence of CRS or ICANS was not significantly associated with age, LDH, ECOG, FLIPI, or prior CAR-T. Conclusions: In this diverse, heavily pretreated real-world cohort, 61% of patients were aged ≥65 years. Bispecific antibodies for R/R FL demonstrated high response rates, favorable survival outcomes, lower rates of cytokine release syndrome—primarily due to fewer grade ≥2 events—and ICANS rates comparable to those observed in pivotal clinical trials, supporting their use across heterogeneous populations, including very elderly patients.