Luminari, Stefano

Abstract 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.

ABSTRACT The characteristics at diagnosis and clinical course of primary extranodal follicular lymphoma (EFL) have not been extensively described. The International Extranodal Lymphoma Study Group (IELSG) conducted an international retrospective survey aimed to describe the clinical features at diagnosis and the outcomes of FL cases with a clinically dominant extranodal component. The dataset included 605 pathologically reviewed cases from 19 different countries, and their outcomes were compared to those of nodal follicular lymphomas. The two most common presentation sites for EFL were the skin ( n = 334) and the gastrointestinal tract ( n = 72), with 22 cases having primary duodenal localization. These subsets exhibited unique features at diagnosis and significantly different overall survival (OS) patterns. After a median follow‐up of 5.5 years, primary cutaneous lymphomas showed a superior outcome [10‐year OS: 89% (95% CI, 83%–93%)], while primary gastrointestinal lymphomas had an intermediate outcome [10‐year OS: 79% (95% CI, 59%–90%)]. Among the gastrointestinal lymphomas, primary duodenal lymphomas tended toward the best outcome [10‐year OS: 95% (95% CI, 69%–99%)]. Other primary extranodal sites had inferior outcomes [10‐year OS: 59% (95% CI, 48%–68%)], similar to primary nodal lymphomas [10‐year OS: 57% (95% CI, 49%–64%)]. These findings support the identification of specific primary FL localizations as distinct entities with particular clinical and biological characteristics.