7076 Background: Odronextamab, an off-the-shelf CD20×CD3 bispecific antibody, has shown compelling efficacy (objective response rate [ORR] 80%, complete response [CR] rate 73%) and a generally manageable safety profile in pts with heavily pretreated R/R FL in the single-arm ELM-2 trial (NCT03888105; Villasboas, et al. ASH 2023). We evaluated outcomes in pts with R/R FL treated with currently available third-line or later (3L+) therapies in a real-world setting (FLORA; NCT05338879) to better evaluate the results from ELM-2 in the absence of a randomized control arm. This is the first real-world study in 3L+ FL that evaluated scans from 100% of the cohort. Methods: FLORA is a multicenter, retrospective, observational study, using electronic medical record or research databases, of pts with R/R FL who have received ≥2 prior lines of therapy (LoTs; including an anti-CD20 and an alkylator) and initiated 3L+ systemic therapy for FL between January 1, 2015 and December 31, 2020. After applying similar eligibility criteria to those in the ELM-2 trial, inverse-probability of treatment weighting (IPTW) was used to balance key prognostic characteristics between the trial and the real-world cohorts. Pts were followed from the start of qualifying LoT until death, end of study (December 31, 2021), or lost to follow-up, whichever occurred first. The primary endpoint was ORR assessed by independent central review (ICR). Secondary endpoints included ICR-assessed CR rate, disease control rate (DCR), progression-free survival (PFS), duration of response (DOR), and overall survival (OS) (see Bachy, et al. ASH 2022). Results: Pts in FLORA (N=100) generally had less severe disease than trial pts prior to IPTW. The most commonly used regimens were chemotherapy + anti-CD20, chemotherapy alone, and anti-CD20 + immunomodulatory agent. The IPTW cohort had a median age of 61 y, 59% POD24, 56% high FLIPI, 60% chemo-immuno refractory, 73% refractory to last LoT, and median (range) prior LoT: 3 (2–8). In the IPTW cohort, ORR was 52%, CR 31%, and DCR 62%. Median PFS (mPFS) was 11.5 mo, median OS was 26.1 mo, and median DOR (mDOR; responders in IPTW cohort: n=54) was 28.2 mo. Given the lack of regular scans in routine practice (37% of responders did not have any subsequent ICR assessment after CR/PR), sensitivity analysis that considered subsequent treatment as a progression event resulted in shorter mDOR (8.1 mo) and mPFS (7.2 mo). Conclusions: Pts in the FLORA study had markedly lower response rates than those in the R/R FL cohort of ELM-2. This study also showed that most pts still received an anti-CD20–based regimen in 3L+ in routine practice, highlighting the need for treatment options with different mechanisms of action that provide deep and durable responses and improve outcomes in this pt population. Clinical trial information: NCT05338879 .