Dynamics of complete responses (CRs) in patients with relapsed or refractory follicular lymphoma (R/R FL) treated with odronextamab in the ELM-2 study.

Complete response (CR) is an important treatment goal in follicular lymphoma (FL). In relapsed or refractory (R/R) FL, CR rates decline, and disease progression accelerates with each treatment line, with particularly poor outcomes in patients with high-risk features. Odronextamab, a CD20 × CD3 bispecific antibody, demonstrated deep, durable responses and generally manageable safety in R/R FL in the Phase 2 ELM-2 study (NCT03888105); we present an exploratory analysis in patients who attained a CR. Patients received intravenous odronextamab with step-up dosing in Cycle 1, 80 mg weekly in Cycles 2-4, then 160 mg once every 2 weeks until disease progression or other protocol-defined reason for discontinuation. Patients with CR lasting ≥9 months switched to dosing once every 4 weeks. Overall, 73.4% (94/128) of patients attained CR, 93.6% (88/94) by first response assessment (~Week 12). Median time to CR was 2.7 months (range 2.3-7.9). Median duration of CR was 25.1 months (95% confidence interval [CI] 20.5-not evaluable [NE]) overall and 23.7 months (18.2-NE) in patients with high-risk features. Overall, 79.5% (35/44) of patients who switched to Q4W dosing maintained CR at last assessment. Patients with low/undetectable CD20 expression by immunohistochemistry (<10% CD20+ cells) or RNA sequencing (messenger RNA < 500 transcripts per million) could achieve CR. Median progression-free survival was 27.8 months (95% CI 23.0-NE) in patients with CR and not reached in those with undetectable circulating tumor DNA at Week 12. Treatment-emergent adverse events (TEAEs) led to treatment discontinuation in 16.0% of patients with CR; the most common TEAE was cytokine release syndrome (56.4%). This generally manageable safety profile and the sustainability of CRs support odronextamab as a potential long-term treatment for heavily pretreated R/R FL.