Background: Goals of patient-centered care for management of relapsed or refractory follicular lymphoma (R/R FL) are to improve clinical outcomes while maintaining or improving health-related quality of life (HRQoL). In ELM-2 (NCT03888105), a Phase 2, open-label, multicohort, multicenter study, odronextamab monotherapy demonstrated high and durable complete response rates and generally manageable safety in patients with R/R FL. We report here, for the first time, patient-reported outcome (PRO) results from ELM-2 in patients with R/R FL.

Methods: Patients with R/R FL Grade 1-3a received odronextamab IV at 80 mg weekly in 21-day cycles in Cycles (C) 1-4. Optimization of the step-up regimen to mitigate cytokine release syndrome (CRS) was reported previously. Odronextamab was administered with steroid prophylaxis and step-up doses of 0.7/4/20 mg in C1, then 80 mg on Days 1, 8, and 15 of C2-4. After C4, odronextamab maintenance continued at 160 mg every 2 weeks until disease progression or unacceptable toxicity. Patients with durable complete response (≥9 months) switched to dosing every 4 weeks. Patients completed EORTC QLQ-C30, FACT-Lym, and EQ-5D-3L questionnaires at Weeks 1 (baseline), 2, 3, 4, and 10, then every 8 weeks for the remainder of the first year and every 12 weeks in the second year. Results here focus on six key PRO scales: EORTC QLQ-C30 Global Health Status/Quality of Life (GHS/QOL), physical functioning (PF), role functioning (RF), and fatigue; FACT-Lym lymphoma subscale (LymS); and EQ-5D-3L visual analog score (VAS). Longitudinal analyses using mixed models for repeated measures (MMRM) were conducted through Week 50 (the last visit with ≥10 patients with PRO data). Changes from baseline were considered statistically significant if the 95% confidence interval did not contain zero. No adjustment for multiplicity was performed, hence all statistical significance is nominal. Published ranges for minimum important difference (MID) to define clinically meaningful changes are: EORTC QLQ-C30 scales, 10 points; FACT-Lym LymS, 2.9-5.4 points; and EQ-5D-3L VAS, 7-12 points. For responder and time to definitive deterioration (TTDD) analyses, the upper end of these published MID ranges was used to define deterioration or improvement.

Results: At the ELM-2 interim data cutoff on 31-Jan-2023, 140 patients with R/R FL Grade 1-3a had received at least 1 dose of odronextamab. Median age was 60.5 years (range: 22-84), with 38.6% ≥65 years, 52.9% male, 57.1% White, 32.1% Asian, 52.2% ECOG=0, and 47.1% ECOG=1. Median duration of follow-up was 26.6 months (range: 6.2-37.5). PRO completion rates for EORTC-QLQ-C30, FACT-Lym, and EQ-5D-3L were high at baseline and remained high for all assessments through Week 50. At baseline, moderate levels of general health (GHS/QoL) and high levels of functioning (PF and RF) were observed that were higher (better) than reference values for general cancer or non-Hodgkin's Lymphoma (NHL). Fatigue scores at baseline were lower (less symptoms) than reference values for general cancer or NHL. EORTC QLQ-C30 GHS/QOL, PF, RF, and fatigue scores were maintained from baseline through Week 50 (Table). For EQ-5D-3L VAS, the overall estimated mean changes from baseline improved statistically significantly but did not reach MID thresholds (Table). For FACT-Lym LymS, overall estimated mean change from baseline statistically significantly improved, and scores improved statistically significantly from Weeks 10 to 42 (except Week 34), with clinically meaningful improvements at Weeks 26 and 42 (Figure). The proportion of patients reporting meaningful improvement or stability across the six scales was higher than the proportion reporting meaningful worsening through Week 50 (Table). The median TTDD for EORTC-QLQ-C30 GHS/QoL was 22.41 (95% CI: 14.59 to not yet reached) months, corresponding to the median PFS. Median TTDD was not reached for EORTC QLQ-C30 PF, FACT-Lym LymS, and EQ-5D-3L VAS scales.

Conclusions: For patients with R/R FL, patient-reported HRQoL results were favorable during odronextamab treatment until disease progression, with no detriments on patient-reported symptoms, functioning, and overall quality of life. These results complement encouraging clinical efficacy, durability of responses, and tolerability observed in this highly refractory patient population and support the future role of odronextamab in the management of patients with R/R FL.

Tessoulin:Gilead: Honoraria; Abbvie: Honoraria; Kite: Honoraria; Incyte: Honoraria. Taszner:Takeda: Consultancy; F. Hoffmann-La Roche Ltd: Consultancy. Kim:F. Hoffmann-La Roche Ltd: Consultancy; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Uncompensated relationship; Regeneron: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Uncompensated relationship; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; IMBDx, Inc.: Honoraria, Speakers Bureau; Boryung: Consultancy, Other: Uncompensated relationship; BeiGene: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Consultancy, Honoraria, Other: Uncompensated relationship, Research Funding; Amgen: Honoraria; MedImmune: Consultancy, Honoraria, Other: Uncompensated relationship; Yuhan: Consultancy; Samsung Bioepis: Consultancy. Novelli:Mundipharma: Consultancy; Novartis: Research Funding. Tucker:Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria; Immunovant: Consultancy; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria. Walewski:Gilead: Honoraria; GSK: Research Funding; Roche: Consultancy, Honoraria, Research Funding; Amgen: Honoraria; Novartis: Consultancy, Honoraria, Research Funding; Servier: Honoraria; Takeda: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria. Chong:Regeneron Pharmaceuticals, Inc.: Research Funding; Pharmacyclics: Research Funding; Merck Serono: Research Funding; AstraZeneca: Research Funding; Bayer: Research Funding; HutchMed: Research Funding; BMS: Membership on an entity's Board of Directors or advisory committees, Research Funding; Incyte: Research Funding; Morphosys: Research Funding; Isofol: Research Funding; Servier: Research Funding; Amgen: Research Funding. Bachy:Takeda: Honoraria; Kite, a Gilead Company: Honoraria, Other: Personal Fees; Hospices Civils de Lyon Claude Bernard Lyon 1 University: Current Employment; Incyte: Honoraria; Pfizer: Honoraria, Other: Personal Fees; Amgen: Research Funding; Novartis: Honoraria, Other: Personal Fees; Roche: Consultancy, Honoraria; Bristol Myers Squibb: Honoraria, Other: Personal Fees, Research Funding. Guidez:Gilead/Kite: Honoraria; Astra-Zeneca: Honoraria; Incyte: Honoraria; Takeda: Honoraria. Jagadeesh:AstraZeneca: Research Funding; ATARA Biotherapeutics: Research Funding; Trillium Pharmaceuticals: Research Funding; Seagen: Research Funding; MEI Pharma: Research Funding; Regeneron Pharmaceuticals: Research Funding; LOXO Pharmaceuticals: Research Funding; Debio Pharma: Research Funding; Affimed: Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Membership on an entity's Board of Directors or advisory committees. Iskierka-Jazdzewska:Janssen: Honoraria; Novartis: Honoraria; AstraZeneca: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria. Tani:Abbvie, Jansen-Cilag, Incyte: Membership on an entity's Board of Directors or advisory committees. Cai:Regeneron: Current Employment, Current holder of stock options in a privately-held company. Ivanescu:IQVIA: Current Employment. Reaney:IQVIA: Consultancy, Current equity holder in private company. Chaudhry:Regeneron: Current Employment, Current holder of stock options in a privately-held company. Mohamed:Regeneron: Current Employment, Current equity holder in publicly-traded company, Patents & Royalties. Ambati:Regeneron: Current Employment, Current holder of stock options in a privately-held company. Harnett:Regeneron Pharmaceuticals, Inc.: Current Employment, Current equity holder in publicly-traded company. Chi:Regeneron: Current Employment, Current holder of stock options in a privately-held company. Luminari:Regeneron Pharmaceuticals, Inc.: Membership on an entity's Board of Directors or advisory committees; Kite: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Janssen Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Beigene: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees.

Odronextamab, a CD20xCD3 bispecific antibody, for the treatment of patients with relapsed/refractory follicular lymphoma.

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2023
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