Real-World Comparison Favors Odronextamab in R/R Follicular Lymphoma

Odronextamab (Ordspono) monotherapy demonstrated improved response rates and favorable survival outcomes compared with third-line or later real-world systemic therapies in patients with relapsed/refractory follicular lymphoma (R/R FL), according to a post-hoc comparative effectiveness analysis published in Leukemia & Lymphoma.¹

The analysis, which aimed to contextualize data from the phase 2 ELM-2 trial (NCT03888105) with the real-world FLORA observational cohort (NCT05338879), provides additional insights on the activity of the CD20xCD3 bispecific antibody in later-line FL, a setting characterized by diminishing responses to conventional therapies.

After statistical weighting to balance baseline characteristics, odronextamab was associated with higher objective and complete response rates. The objective response rate with odronextamab was 80.5% vs 52.7% in the real-world cohort (OR, 3.75; 95% CI, 1.98-7.11). Complete response rates were 73.4% vs 33.6%, respectively (OR, 5.39; 95% CI, 2.76-10.53).

Several time-to-event end points also favored odronextamab over systemic therapies. Median progression-free survival was 20.7 months with odronextamab and 11.5 months with real-world therapies (HR, 0.76; 95% CI, 0.46-1.24). Event-free survival and time to next treatment or death also favored odronextamab, with hazard ratios of 0.52 (95% CI, 0.36-0.77) and 0.49 (95% CI, 0.33-0.72), respectively. Overall survival was not reached in the odronextamab group vs 26.2 months in the systemic therapies group (HR, 0.60; 95% CI, 0.37-0.97).

“Despite FLORA’s limited sample size, these data further support odronextamab monotherapy for [third-line or later] R/R FL,” the authors concluded.

About Odronextamab and Clinical Implications

Odronextamab is a bispecific antibody targeting CD20 on B cells and CD3 on T cells, facilitating T-cell–mediated cytotoxicity against malignant B cells. The phase 1 ELM-1 (NCT02290951) and phase 2 ELM-2 trials evaluated the agent in patients with R/R B-cell non-Hodgkin lymphoma, including FL.²

In the dose-escalation and -expansion cohorts of ELM-1, odronextamab demonstrated preliminary antitumor activity across multiple histologies, supporting further investigation in later-phase studies.³ The ELM-2 trial subsequently assessed fixed-duration and response-adapted dosing strategies in heavily pretreated populations. Among patients with R/R FL, previously reported results from ELM-2 showed high complete response rates and durable remissions, with a substantial proportion of responders maintaining disease control beyond 18 months.⁴

The safety profile of odronextamab has been characterized by immune-mediated toxicities consistent with T-cell–engaging therapies. Cytokine release syndrome has been the most commonly observed adverse event, generally occurring during initial dosing and managed with step-up dosing regimens and supportive care. Neurologic events, including immune effector cell–associated neurotoxicity syndrome (ICANS), have been reported less frequently. Hematologic toxicities, including neutropenia, also remain clinically relevant in this patient population.

Bispecific antibodies, including odronextamab, represent an emerging class of “off-the-shelf” immunotherapies that may offer logistical advantages over cellular therapies such as chimeric antigen receptor (CAR) T-cell therapy. These advantages include broader accessibility and shorter time to treatment initiation, which are key facilitators for use in community settings.

However, regulatory progress for odronextamab has been mixed. In August 2025, the FDA declined to approve odronextamab as a treatment for R/R FL for a second time due to issues with a site inspection, rather than clinical efficacy or safety concerns. Ongoing studies, including randomized trials in earlier lines of therapy, are expected to further define the role of odronextamab within the evolving treatment landscape for FL.

REFERENCES

1. Bachy E, Harnett J, Prochazka K, et al. Comparative effectiveness of odronextamab monotherapy versus real-world systemic therapies in R/R follicular lymphoma. Leuk Lymphoma. 2026;67(4):907-918. doi:10.1080/10428194.2026.2619500

2. A Study to Assess the Anti-Tumor Activity and Safety of Odronextamab in Adult Patients With B-cell Non-Hodgkin Lymphoma Who Have Been Previously Treated With Other Cancer Therapies (ELM-2). ClinicalTrials.gov. Updated October 15, 2025. Accessed April 22, 2026. https://clinicaltrials.gov/study/NCT03888105

3. Topp MS, Matasar M, Allan JN, et al. Odronextamab monotherapy in R/R DLBCL after progression with CAR T-cell therapy: primary analysis of the ELM-1 study. Blood. 2025;145(14):1498-1509. doi:10.1182/blood.2024027044

4. Ayyappan S, Kim WS, Kim TM, et al. Final analysis of the phase 2 ELM-2 study: odronextamab in patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL). Blood. 2023;142(Supplement 1):436-436. doi:10.1182/blood-2023-179818