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4461 Odronextamab Demonstrates Durable Complete Responses in Patients with Diffuse Large B-Cell Lymphoma (DLBCL) Progressing after CAR-T Therapy: Outcomes from the ELM-1 Study

Program: Oral and Poster Abstracts
Session: 626. Aggressive Lymphomas: Prospective Therapeutic Trials: Poster III
Hematology Disease Topics & Pathways:
Research, clinical trials, Lymphomas, non-Hodgkin lymphoma, Clinical Research, Diseases, Lymphoid Malignancies
Monday, December 11, 2023, 6:00 PM-8:00 PM

Jennifer L. Crombie, MD1*, Matthew Matasar, MD, MS2, Max S. Topp, MD3*, John N. Allan, MD2, Jeffrey A. Barnes4*, Jon E. Arnason, MD5, Jean-Marie Michot6*, Neta Goldschmidt7*, Susan M. O'Brien8, Uri Abadi, MD9,10*, Irit Avivi Mazza, MD11*, Jessica Cai12*, Dina M. Flink12, Min Zhu12*, Jurriaan Brouwer-Visser12*, Hesham Mohamed12, Aafia Chaudhry12, Srikanth Ambati12* and Steve M Ansell13

1Dana Farber Cancer Institute, Boston, MA
2Rutgers Cancer Institute of New Jersey, New Brunswick, NJ
3Universitätsklinikum Würzburg, Würzburg, Germany
4Massachusetts General Hospital Cancer Center, Boston, MA
5Beth Israel Deaconess Medical Center, Boston, MA
6Gustave Roussy Cancer Campus, Villejuif, France
7Hadassah Medical Center and Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel
8Chao Family Comprehensive Cancer Center, University of California, Irvine, Orange, CA
9Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
10Hematology Institute, Meir Medical Center, Kfar Saba, Israel
11Ichilov University Hospital, Tel-Aviv, Israel
12Regeneron Pharmaceuticals, Inc., Tarrytown, NY
13Mayo Clinic, Rochester, MN


Chimeric antigen receptor (CAR) T-cell therapies have recently been established as an important option for the management of relapsed/refractory (R/R) DLBCL. However, real-world studies suggest that approximately half of all patients (pts) receiving commercial CAR-T therapies will relapse within 6 months. These pts have a poor prognosis, with estimated overall survival (OS) of only 5 months, indicating a significant unmet need. Odronextamab is a novel, off-the-shelf, CD20×CD3 bispecific antibody that has demonstrated activity in both R/R follicular lymphoma and R/R DLBCL. We have previously reported encouraging results with odronextamab from the Phase 1 ELM-1 study (NCT02290951) in pts with R/R DLBCL post CAR-T therapy (Bannerji R, et al. Lancet Haematol. 2022). These results were consistent with the antitumor activity seen in pts with R/R DLBCL from the Phase 2 ELM-2 study (Kim WS, et al. ASH 2022). Here, we present an updated analysis of outcomes in a prespecified cohort of post CAR-T patients from ELM-1.


Intravenous odronextamab was administered weekly in 21-day cycles during Cycles (C) 1–4. Revisions to the step-up regimen were reported previously (Bannerji R, et al. Lancet Haematol. 2022). Odronextamab was administered with steroid prophylaxis and step-up doses of 0.7/4/20 mg during C1 to mitigate the risk of cytokine release syndrome (CRS), followed by 160 mg on Days (D) 1, 8, and 15 of C2–4. After C4, odronextamab maintenance treatment continued at 320 mg every 2 weeks until disease progression or unacceptable toxicity. Those pts who achieved a complete response (CR) that was durable for ≥9 months transitioned to dosing with 320 mg every 4 weeks. The primary endpoint was objective response rate (ORR), assessed by independent central review (ICR) according to the Lugano classification. Key secondary endpoints included duration of response (DoR), progression-free survival (PFS), and OS. Immune biomarker assessment was an exploratory endpoint.


As of Dec 20, 2022, 46 pts were treated (safety-evaluable), with 44 pts evaluable for efficacy. For safety-evaluable pts, median age was 63 years (range 27–82), 67% male, 74% Ann Arbor stage III–IV, and 72% were refractory to CAR-T therapy administered in any prior line. 44 pts were evaluable for efficacy after 4.9 months median duration of follow-up. The ORR and CR rate by ICR were 48% (21/44) and 30% (13/44), respectively. Responses were durable, and both median DoR and median duration of CR were not reached. The probability of maintaining a response for 12 months was 62% and the probability of maintaining a CR for 9 months was 86%. A responder analysis of the subgroup of pts who achieved a CR will be presented.

The CAR-T treated pts with DLBCL who were evaluable for biomarker analysis (n=10) had lower T-cell counts at baseline compared with CAR-T naive DLBCL pts (n=41 comparable pts who received odronextamab in ELM-2), yet the fold-change of T-cell expansion at C4D15 was greater in CAR-T treated pts versus CAR-T naive pts. T-cell dynamics, such as changes in activation, exhaustion, and memory subsets, will be presented.

Safety was generally consistent with that previously reported. Six (13%) pts permanently discontinued odronextamab due to a treatment-emergent AE (device-related infection, pneumonia, dysphagia, gait disturbance, leukemia, and encephalopathy [n=1 each]). The most common treatment-emergent AE was CRS (any grade, 52%). The highest grade of CRS reported was Grade 2, and low-grade CRS events occurred in 46% of pts with the 0.7/4/20 mg step-up regimen. No cases of ICANS were reported in pts with the 0.7/4/20 mg regimen. Grade ≥3 infections occurred in 10 (22%) pts, with no Grade 5 events. No cases of tumor flare were reported.


Odronextamab monotherapy demonstrates encouraging antitumor activity in heavily pretreated pts who have progressed after CAR-T therapy, with a generally manageable safety profile. Durable CRs were achieved in this difficult-to-treat setting. These data support the potential role of odronextamab in the treatment paradigm for R/R DLBCL. Further studies to evaluate the optimal sequencing and combinations of odronextamab with CAR-T therapy are warranted.

Disclosures: Crombie: ADC Therapeutics: Consultancy; Merck: Research Funding; Genetech/Roche: Research Funding; Dana-Farber Cancer Institute: Current Employment; Abbvie: Research Funding; Bayer: Research Funding; Kite Pharma: Consultancy; MorphoSys/Incyte: Consultancy; Karyopharm: Consultancy; Seagen: Consultancy; Genmab: Consultancy. Matasar: Seattle Genetics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Consultancy, Honoraria; Teva: Consultancy; Genentech, Inc.: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics: Honoraria, Research Funding; Immunovaccine Technologies: Research Funding; Janssen: Honoraria, Research Funding; Juno: Consultancy; Regeneron: Honoraria, Other: Stipends; Kite: Honoraria, Other: Stipends; Immunovaccine Technologies: Honoraria; Epizyme: Other: Stipends; Celegene: Honoraria, Other: Stipends; BMS: Honoraria, Other: Stipend; Bayer: Consultancy, Honoraria, Research Funding; AstraZeneca: Honoraria, Other: Stipend; Merck: Current equity holder in private company; ADC Therapeutics: Consultancy, Honoraria, Other: Stipend; Seagen: Honoraria, Other: stipends. Topp: Takeda: Research Funding; GenMab: Consultancy; Regeneron Pharmaceuticals, Inc.: Consultancy, Research Funding; Janssen: Consultancy, Other: Travel support; AbbVie: Consultancy; Kite, a Gilead Company: Consultancy, Other: Travel support, Research Funding; Bristol Myers Squibb: Consultancy, Research Funding; Roche: Consultancy, Research Funding; AstraZeneca: Consultancy, Research Funding. Allan: TG Therapeutics, Inc: Consultancy, Research Funding; Pharmacyclics LLC: Consultancy, Speakers Bureau; Lava Therapeutics: Consultancy; Adaptive Biotechnologies: Consultancy; Lilly: Consultancy; ADC Therapeutics SA: Consultancy; Janssen: Consultancy, Research Funding, Speakers Bureau; AbbVie: Consultancy, Honoraria, Speakers Bureau; AstraZeneca: Consultancy, Honoraria; BeiGene: Consultancy, Honoraria, Research Funding, Speakers Bureau; Epizyme: Consultancy; Genentech, Inc.: Consultancy, Research Funding. Arnason: Bristol Myers Squibb: Speakers Bureau. Michot: AstraZeneca: Honoraria, Other: Non-financial support; Bristol Myers Squibb: Honoraria, Other: Non-financial support; Celgene: Honoraria, Other: Non-financial support; Janssen: Honoraria, Other: Non-financial support; Gilead Sciences: Other: Non-financial support; Novartis: Other: Non-financial support; Roche: Other: Non-financial support. O'Brien: Astrazeneca: Consultancy; Beigene: Consultancy, Research Funding; Lilly: Consultancy, Research Funding; Janssen: Consultancy; Johnson & Johnson: Consultancy; Pfizer: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; Regeneron: Research Funding; Abbvie: Consultancy. Avivi Mazza: AbbVie: Honoraria. Cai: Regeneron: Current Employment, Current holder of stock options in a privately-held company. Flink: Regeneron: Current Employment, Current equity holder in publicly-traded company. Zhu: Regeneron: Current Employment, Current equity holder in publicly-traded company. Brouwer-Visser: Regeneron: Current Employment, Current equity holder in publicly-traded company. Mohamed: Regeneron: Current Employment, Current equity holder in publicly-traded company, Patents & Royalties. Chaudhry: Regeneron: Current Employment, Current holder of stock options in a privately-held company. Ambati: Regeneron: Current Employment, Current holder of stock options in a privately-held company. Ansell: ADC Therapeutics: Research Funding; Pfizer: Research Funding; AstraZeneca: Research Funding; Affimed: Research Funding; Takeda: Research Funding; SeaGen: Research Funding; BMS: Research Funding; Regeneron Pharmaceuticals, Inc.: Research Funding.

OffLabel Disclosure: Odronextamab, a CD20xCD3 bispecific antibody, for the treatment of patients with relapsed/refractory diffuse large B-cell lymphoma

*signifies non-member of ASH