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Clinical Trial
. 2025 Apr 3;145(14):1498-1509.
doi: 10.1182/blood.2024027044.

Odronextamab monotherapy in R/R DLBCL after progression with CAR T-cell therapy: primary analysis of the ELM-1 study

Max S Topp  1 , Matthew Matasar  2 , John N Allan  3 , Stephen M Ansell  4 , Jeffrey A Barnes  5 , Jon E Arnason  6 , Jean-Marie Michot  7 , Neta Goldschmidt  8 , Susan M O'Brien  9 , Uri Abadi  10   11 , Irit Avivi  12 , Yuan Cheng  13 , Dina M Flink  13 , Min Zhu  13 , Jurriaan Brouwer-Visser  13 , Aafia Chaudhry  13 , Hesham Mohamed  13 , Srikanth Ambati  13 , Jennifer L Crombie  14
Affiliations
Clinical Trial

Odronextamab monotherapy in R/R DLBCL after progression with CAR T-cell therapy: primary analysis of the ELM-1 study

Max S Topp et al. Blood. .

Abstract

Patients with relapsed/refractory diffuse large B-cell lymphoma progressing after chimeric antigen receptor T-cell (CAR-T) therapy have dismal outcomes. The prespecified post-CAR-T expansion cohort of the ELM-1 study investigated the efficacy and safety of odronextamab, a CD20×CD3 bispecific antibody, in patients with disease progression after CAR-Ts. Sixty patients received IV odronextamab weekly for 4 cycles followed by maintenance until progression. The primary end point was objective response rate (ORR) by independent central review. The median number of prior lines of therapy was 3 (range, 2-9), 71.7% were refractory to CAR-Ts, and 48.3% relapsed within 90 days of CAR-T therapy. After a median follow-up of 16.2 months, ORR and complete response (CR) rate were 48.3% and 31.7%, respectively. Responses were similar across prior CAR-T products and time to relapse on CAR-T therapy. Median duration of response was 14.8 months and median duration of CR was not reached. Median progression-free survival and overall survival were 4.8 and 10.2 months, respectively. The most common treatment-emergent adverse event was cytokine release syndrome (48.3%; no grade ≥3 events). No cases of immune effector cell-associated neurotoxicity syndrome were reported. Grade ≥3 infections occurred in 12 patients (20.0%), 2 of which were COVID-19. Odronextamab monotherapy demonstrated encouraging efficacy and generally manageable safety, supporting its potential as an off-the-shelf option for patients after CAR-T therapy. This trial was registered at www.clinicaltrials.gov as #NCT02290951.

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Conflict of interest statement

Conflict-of-interest disclosure: M.S.T. reports consultancy for AbbVie, AstraZeneca, BeiGene, Genmab, Incyte, Janssen, and Kite; and research funding from AstraZeneca, Kite, Regeneron Pharmaceuticals, Inc., and Roche. M.M. reports consultancy for Bayer, Genentech, GM Biosciences, Johnson & Johnson, Pharmacyclics, Roche, and Seattle Genetics; research funding from Bayer, Genentech, GM Biosciences, ImmunoVaccine Technologies, Johnson & Johnson, Pharmacyclics, Roche, and Seattle Genetics; honoraria from ADC Therapeutics, AstraZeneca, Bayer, Bristol Myers Squibb, Celgene, Epizyme, Genentech, IMV Therapeutics, Johnson & Johnson, Kite, Pharmacyclics, Regeneron Pharmaceuticals, Inc., Roche, Pfizer, Seattle Genetics, and Takeda; and membership on an entity’s board of directors or advisory committees for Allogene, Genentech, Genmab, and Merck. J.N.A. reports consultancy for AbbVie, Adaptive Biotechnologies, ADC Therapeutics, AstraZeneca, BeiGene, Genentech, Janssen, Eli Lilly, NeoGenomics, and Pharmacyclics; and research funding from BeiGene, Celgene/Bristol Myers Squibb, Genentech, and Janssen. S.M.A. reports trial research funding from ADC Therapeutics, Affimed, AstraZeneca, Bristol Myers Squibb, Pfizer, Regeneron Pharmaceuticals, Inc., and Takeda. J.E.A. reports speaker’s fee from Regeneron Pharmaceuticals, Inc. J.-M.M. reports consultancy for Ideogen, GlaxoSmithKline, Gilead, Merck, Regeneron Pharmaceuticals, Inc., and Therakos/Mallinckrodt; research funding from Astex Pharmaceuticals; and travel support from Beigene, Bristol Myers Squibb, GlaxoSmithKline, and Regeneron Pharmaceuticals Inc. S.M.O. reports consultancy for AbbVie, AstraZeneca, Autolus, BeiGene, Bristol Myers Squibb, Eli Lilly, GlaxoSmithKline, Janssen Oncology, Johnson & Johnson, Loxo Oncology, Merck, Pfizer, and Pharmacyclics; and research funding from Alliance, Caribou Biosciences, Nurix Therapeutics, and Regeneron Pharmaceuticals, Inc. Y.C., D.M.F., M.Z., J.B.-V., A.C., H.M., and S.A. hold stock or stock options for, and are employees of, Regeneron Pharmaceuticals, Inc. J.L.C. reports consultancy for Genmab, Incyte, Karyopharm Therapeutics, Kite Pharma, MorphoSys, Regeneron Pharmaceuticals, Inc., and Seagen; funding from AbbVie, Bayer, Genentech/Roche, and Merck; and employment with the Dana-Farber Cancer Institute. The remaining authors declare no competing financial interests.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Sankey plot of responses by independent central review at weeks 5, 12, and 36. Deeper responses were observed at week 12, with 8 of 14 patients with PR at week 5 achieving CR, and 3 of 14 maintaining PR; 4 of 18 patients with SD at week 5 achieving CR and 6 of 18 achieving PR. Additionally, 2 patients with PR at week 12 achieved CR at week 36.
Figure 2.
Figure 2.
Time-to-event outcomes. DOR and DOCR by independent central review (ICR) (A), PFS by response by ICR (B), and OS by response (C). DOCR, duration of complete response.
Figure 3.
Figure 3.
T-cell counts and fitness on odronextamab treatment. Fold changes in CD4 T-cell (A) and CD8 T-cell (B) counts from baseline to week 4/5 and week 14 by best overall response. Changes in IFN-γ (C) and TNF-α (D) upon ex vivo stimulation. 2H, 2 hours; D, day; NA, not available; W, week.
Figure 4.
Figure 4.
Ratio of TEM to naïve T cells at baseline and on treatment by best overall response. Ratio of TEM CD4 to naïve CD4 T cells (A) and TEM CD8 to naïve CD8 T cells (B).
See this image and copyright information in PMC

Comment in

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