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3118 Long-Term Efficacy and Safety of Odronextamab in Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL): Pooled Analysis from the ELM-1 and ELM-2 Studies

Program: Oral and Poster Abstracts
Session: 627. Aggressive Lymphomas: Pharmacologic Therapies: Poster II
Hematology Disease Topics & Pathways:
Research, Clinical trials, Lymphomas, Non-Hodgkin lymphoma, Clinical Research, Diseases, Lymphoid Malignancies
Sunday, December 8, 2024, 6:00 PM-8:00 PM

John N. Allan, MD1, Jennifer L. Crombie, MD2, Matthew Matasar, MD, MS3, Max S. Topp4*, Jan Walewski5*, Tae Min Kim, MD, PhD6*, Won-Seog Kim7*, Yuan Cheng8*, Dina Flink8, Bertha Fearon Chalet8*, Hesham Mohamed8, Srikanth Ambati8, Aafia Chaudhry8 and Jon E. Arnason, MD9

1Weill Cornell Medicine, New York, NY
2Dana-Farber Cancer Institute, Boston, MA
3Division of Blood Disorders, Rutgers Cancer Institute and RWJBarnabas Health, New Brunswick, NJ
4Universitätsklinikum Würzburg, Würzburg, Germany
5Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie Państwowy Instytut Badawczy, Warszawa, Poland
6Seoul National University Hospital, Seoul, Korea, Republic of (South)
7Samsung Medical Center, Center for Hematologic Malignancy, Seoul, Korea, Republic of (South)
8Regeneron Pharmaceuticals, Inc., Tarrytown, NY
9Beth Israel Deaconess Medical Center, Boston, MA

Introduction
Odronextamab, a novel, investigational, CD20×CD3 bispecific antibody, has demonstrated compelling efficacy and a generally manageable safety profile in heavily pretreated patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) in the CAR-T–naïve and post–CAR-T therapy settings (Ayyappan S et al. ASH 2023; Crombie J et al. ASH 2023). Here, we report long-term efficacy and safety data for odronextamab from a pooled analysis of the DLBCL post–CAR-T cohort in the ELM-1 study (NCT02290951), which was the only pivotal study of a bispecific antibody with a prespecified cohort dedicated to this population, and the CAR-T–naïve DLBCL cohort in the ELM-2 study (NCT03888105).

Methods
Odronextamab was administered intravenously in 21-day cycles. A step-up dosing regimen with steroid prophylaxis was employed during Cycle 1, followed by 160 mg on Days 1, 8, and 15 of Cycles 2–4. Maintenance therapy consisted of 320 mg every 2 weeks until disease progression or unacceptable toxicity. Patients with durable complete response (CR) for ≥9 months transitioned to dosing every 4 weeks. The primary endpoint was objective response rate (ORR) by independent central review (ICR) using the Lugano classification. Key secondary endpoints included CR rate, duration of response (DOR), progression-free survival (PFS), and overall survival (OS).

Results
The analysis set consisted of a pooled population of 187 patients with R/R DLBCL from ELM-1 (n=60; data cutoff date of January 22, 2024) and ELM-2 (n=127; data cutoff date October 20, 2023). Median duration of follow-up was 23.0 months. Median age was 65.0 years (range 24–88), 61.5% of patients were male, 78.6% had Ann Arbor stage III–IV, 56.7% had an IPI score ≥3, and the median number of prior lines of therapy was 3 (range 2–9). The 60 patients included from ELM-1 had all received prior CAR-T therapy, representing 32.1% of the total pooled population (60/187), and of these, 48.3% (29/60) had relapsed within ≤90 days of initiating CAR-T therapy, and 71.7% (43/60) had CAR-T–refractory disease. Overall, 83.4% of the pooled population had disease that was refractory to the last line of therapy. Median duration of odronextamab exposure was 14.7 weeks; 91.4% (171/187) of the population completed ≥1 cycle, and 59.4% (111/187) completed ≥4 cycles.

ORR and CR rate confirmed by ICR were 50.8% (95/187) and 31.6% (59/187), respectively, and were generally consistent across multiple high-risk subgroups, including the post–CAR-T therapy subgroup. Median DOR was 10.5 months (95% CI 5.4–24.8) and median duration of CR was 36.3 months (95% CI 12.4–not evaluable); the probability of maintaining CR for 36 months was 51.0%. The probability of PFS and OS at 36 months was 17.5% and 27.0%, respectively.

Safety was generally consistent with previous reports. The most common treatment-emergent adverse events (>30% all grades) were cytokine release syndrome (CRS; 52.9%), anemia (35.8%), pyrexia (39.6%), and neutropenia (31.6%). Adverse events led to treatment discontinuation in 25 patients (13.4%). With the optimized 0.7/4/20 mg step-up regimen (n=100), 48.0% of patients (48/100) had CRS events that were Grade (Gr) 1/2, and one Gr 3 CRS event (confounded by pancreatitis) was reported. All CRS events resolved with supportive measures. No immune effector cell-associated neurotoxicity syndrome events were reported with the 0.7/4/20 mg step-up regimen. Gr ≥3 infections occurred in 46 patients (24.6%; Gr 5, n=16 [8.6%]). COVID-19 infections were reported in 30 patients (16.0%), of which Gr 5 was reported in 6 patients (3.2%).


Conclusions
This pooled analysis of patients with R/R DLBCL from the ELM-1 and ELM-2 studies, which represents the largest dataset reported for a bispecific antibody in the third-line or later setting, confirms that with longer follow-up the recommended odronextamab dose retains highly encouraging efficacy. Responses were durable, with a 51% probability of maintaining CR for 3 years. The safety profile was generally consistent with earlier reports and CRS events with the 0.7/4/20 mg step-up dosing regimen were predominantly low grade and generally manageable. Importantly, continued treatment with odronextamab demonstrated no detrimental effects on survival outcomes over a longer follow-up period. Odronextamab may be an important potential option in future management of R/R DLBCL, and Phase 3 trials are ongoing. Updated data will be presented.

Disclosures: Allan: Celgene: Consultancy, Research Funding; AstraZeneca: Consultancy; ADC Therapeutics: Consultancy; BeiGene: Consultancy, Speakers Bureau; Epizyme: Consultancy; TG Therapeutics: Consultancy, Research Funding; Janssen: Consultancy, Research Funding, Speakers Bureau; Genentech: Consultancy, Research Funding; AbbVie: Consultancy, Speakers Bureau; Pharmacyclics LLC, an AbbVie Company: Consultancy, Speakers Bureau. Crombie: Abbvie: Research Funding; Bayer: Research Funding; Genentech/Roche: Research Funding; Merck: Research Funding; Genentech: Consultancy; Genmab/Abbvie: Consultancy; Seagen: Consultancy; Regeneron Pharmaceuticals, Inc.: Consultancy; ADCT: Consultancy. Matasar: Allogene: Membership on an entity's Board of Directors or advisory committees; Immunovaccine Technologies: Research Funding; BMS/Celgene: Honoraria; AstraZeneca: Honoraria; Roche: Consultancy, Honoraria, Research Funding; Pharmacyclics: Consultancy, Honoraria, Research Funding; Genentech: Consultancy, Honoraria, Research Funding; ADC Therapeutics: Honoraria; Genmab: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Consultancy, Honoraria, Research Funding; Kite: Honoraria; Johnson & Johnson: Consultancy, Honoraria, Research Funding; Merck: Current equity holder in publicly-traded company; GM Biosciences: Consultancy, Research Funding; Epizyme: Honoraria; IMV Therapeutics: Honoraria; Pfizer: Honoraria; Regeneron Pharmaceuticals, Inc.: Honoraria; Takeda: Honoraria; Bayer: Consultancy, Honoraria, Research Funding. Topp: Kite, a Gilead Company: Honoraria, Research Funding; Incyte: Consultancy; Roche: Honoraria, Other: Travel Support, Research Funding; AbbVie: Consultancy; Janssen: Consultancy, Honoraria; Autolus Therapeutics: Consultancy; Bristol Myers Squibb: Consultancy, Honoraria; AstraZeneca: Consultancy, Honoraria, Research Funding; Regeneron Pharmaceuticals, Inc.: Honoraria, Research Funding; Universitatsklinikum Wurzburg: Current Employment. Walewski: Polish Myeloma Consortium: Research Funding; Polish Lymphoma Research Group (PLRG): Research Funding; NanoVector: Research Funding; MSD: Consultancy, Research Funding; Karyopharm: Research Funding; MorphoSys: Research Funding; Janssen-Cilag: Research Funding; Incyte: Research Funding; GSK: Research Funding; Gilead: Consultancy, Honoraria, Research Funding; Epizyme: Research Funding; Bristol Myers Squibb/Celgene: Research Funding; AstraZeneca/MedImmune: Research Funding; Regeneron Pharmaceuticals, Inc.: Consultancy, Research Funding; Roche: Honoraria; Seagen: Research Funding; Takeda: Research Funding; TG Therapeutics: Research Funding; Vanda Pharmaceuticals: Research Funding. Kim: BeiGene: Membership on an entity's Board of Directors or advisory committees; Regeneron: Consultancy, Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo, HK inno.N, F. Hoffmann-La Roche Ltd/Genentech, Yuhan: Consultancy; Yuhan: Consultancy; Roche/Genetech: Consultancy; Samsung Bioepis: Consultancy; Takeda: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; IMBDx. Inc.: Consultancy, Honoraria; Novartis: Consultancy; Janssen: Consultancy, Honoraria; Boryung: Consultancy; AstraZeneca/MedImmune: Consultancy. Kim: BeiGene: Research Funding; Donga: Research Funding; Boryong: Research Funding; Sanofi: Research Funding; Kyowa-Kirin: Research Funding; Roche: Research Funding. Cheng: Regeneron Pharmaceuticals, Inc.: Current Employment, Current holder of stock options in a privately-held company. Flink: Regeneron Pharmaceuticals, Inc.: Current Employment, Current holder of stock options in a privately-held company. Fearon Chalet: Regeneron Pharmaceuticals, Inc.: Current Employment, Current holder of stock options in a privately-held company. Mohamed: Regeneron Pharmaceuticals, Inc.: Current Employment, Current holder of stock options in a privately-held company. Ambati: Regeneron Pharmaceuticals, Inc.: Current Employment, Current holder of stock options in a privately-held company. Chaudhry: Regeneron Pharmaceuticals, Inc.: Current Employment, Current holder of stock options in a privately-held company. Arnason: Regeneron Pharmaceuticals, Inc.: Other: Speaker fees; BMS: Other: Speaker fees.

OffLabel Disclosure: Odronextamab, an investigational CD20xCD3 bispecific antibody, for the treatment of patients with relapsed or refractory DLBCL

*signifies non-member of ASH