Odronextamab monotherapy in patients with relapsed/refractory diffuse large B cell lymphoma: primary efficacy and safety analysis in phase 2 ELM-2 trial

The phase 2, multicohort, ongoing ELM-2 study evaluates odronextamab, a CD20×CD3 bispecific antibody, in patients with relapsed/refractory (R/R) B cell non-Hodgkin lymphoma after ≥2 lines of therapy. Here primary analysis of the diffuse large B cell lymphoma (DLBCL) cohort is reported. Patients received intravenous odronextamab in 21-day cycles until progression or unacceptable toxicity, with cycle 1 step-up dosing to mitigate cytokine release syndrome (CRS) risk. The primary endpoint was objective response rate (ORR). Secondary endpoints included complete response (CR) rate, duration of response, progression-free survival (PFS) and overall survival. A total of 127 patients were enrolled. At the 29.9-month efficacy follow-up, the ORR was 52.0% and CR rate was 31.5%. Median durations of response and CR were 10.2 and 17.9 months, respectively. Undetectable minimal residual disease at cycle 4 day 15 was associated with PFS benefit. With a step-up of 0.7 to 4 to 20 mg (n = 60), CRS was the most common treatment-emergent adverse event (53.3% (grade ≥3, 1.7%)). No immune effector cell-associated neurotoxicity syndrome was reported. Infections were reported in 82/127 (64.6%) patients (grade ≥3, 38.6%; coronavirus disease 2019, 18.1% (grade ≥3, 12.6%)). In conclusion, odronextamab showed encouraging efficacy in heavily pretreated R/R DLBCL and generally manageable safety with supportive care. Clinical trial registration: NCT03888105 .

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Nature Cancer
Published
2025-03-17
DOI
https://doi.org/10.1038/s43018-025-00921-6
Citations
36
Primary Topic
CAR-T cell therapy research
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article
Field-Weighted Citation Impact
37.63

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article

Odronextamab monotherapy in patients with relapsed/refractory diffuse large B cell lymphoma: primary efficacy and safety analysis in phase 2 ELM-2 trial

Mary‐Margaret Keating, Wei Zheng, Jurriaan Brouwer‐Visser, Masahiro Takeuchi et al.
36 citations
Nature Cancer
CAR-T cell therapy research
37.63
article

Odronextamab monotherapy in patients with relapsed/refractory diffuse large B cell lymphoma: primary efficacy and safety analysis in phase 2 ELM-2 trial

Mary‐Margaret Keating, Wei Zheng, Jurriaan Brouwer‐Visser, Masahiro Takeuchi, Francesca Gaia Rossi, Li Gao, Antonio M. Gutierrez, Vittorio Ruggiero Zilioli, Ming‐Chung Wang, Francesca Lim, Lori Ann Leslie, Michael Chu, Young Rok, Deepa Jagadeesh, Sylvain Choquet, Shang‐Ju Wu, Sabarish Ayyappan, Jon Arnason, Stefano Luminari, Monica Tani, Srikanth Ambati, Nobuhiko Yamauchi, Ana Jiménez Ubieto, Marco Brociner, Hannah Rose, Parameswaran Venugopal, Aránzazu Alonso, Liqun Zou, Tran‐Der Tan, John Nathan Allan, Holger Hebart, Hesham Mohamed, Tomasz Wróbel, Sami Ibrahimi, Shuhua Yi, Don A. Stevens, Corinne Haïoun, Henry Miles Prince, Michał Taszner, Enrico Capochiani, Agustin Penedo Coello, Junya Kuroda, Isao Yoshida, Yuqin Song, José C. Villasboas, Jae‐Cheol Jo, Tomomi Tobai, Gianluca Gaïdano, Alejandro Martı́n, David Tucker, Nagah Elmusharaf, Cecilia Carpio, Jingxian Cai, Melanie Ufkin, Kuangwen Hsieh, Tatsuro Jo, Thomas Jandl, Shin Yeu Ong, Eva M. González-Barca, Vinod Ganju, Kunihiro Tsukasaki, Franck Morschhauser, Andrea Kühnl, Emmanuel Bachy, Isidro Jarque, Yeung‐Chul Mun, Kenichi Ishizawa, David Cunningham, Jan Walewski, Thomas Weber, Seok‐Goo Cho, Farrukh T. Awan, Ewa Lech-Maranda, Leonardo Flenghi, Johannes Duell, Andreas K. Klein, Gandhi Laurent Damaj, Toshiki Uchida, Yosuke Minami, Sara Miqueleiz, Won Seog Kim, L Bagnato, Catherine Thieblemont, Sung Yong Oh, Junning Cao, Laura Magnano, Raúl Córdoba, Benoît Tessoulin, Elżbieta Iskierka‐Jazdzewska, Dengju Li, Geoffrey Chong, Wanda Knopińska‐Posłuszny, Ou Bai, Tadeusz Robak, Roberta Battistini, Vincent Delwail, Li Mei Poon, Junichiro Yuda, Hirohisa Nakamae, Mingzhi Zhang, Jun Zhu, Caixia Li, Byung‐Soo Kim, Umar Farooq, Tae Min Kim, Qingyuan Zhang, Jin Seok Kim, Hirokazu Nagai, Yoshiaki Ogawa, Jie Jin, Huiqiang Huang, Youhua Chen, Pengcheng He, Xiaoyan Ke, David Lewis, Rafael Andreu, Hyeon-Seok Eom, Pier Luigi Zinzani, Cristina Skert, Su Peng Yeh, Rakhee Vaidya, Ryusuke Yamamoto, Tsai Yun Chen, Youko Suehiro, Wenbin Qian, Aafia Chaudhry, Saleem Shariff, Huilai Zhang, Kamal Bouabdballah, Paul Graf La Rosee
article en
36 citations

Abstract

The phase 2, multicohort, ongoing ELM-2 study evaluates odronextamab, a CD20×CD3 bispecific antibody, in patients with relapsed/refractory (R/R) B cell non-Hodgkin lymphoma after ≥2 lines of therapy. Here primary analysis of the diffuse large B cell lymphoma (DLBCL) cohort is reported. Patients received intravenous odronextamab in 21-day cycles until progression or unacceptable toxicity, with cycle 1 step-up dosing to mitigate cytokine release syndrome (CRS) risk. The primary endpoint was objective response rate (ORR). Secondary endpoints included complete response (CR) rate, duration of response, progression-free survival (PFS) and overall survival. A total of 127 patients were enrolled. At the 29.9-month efficacy follow-up, the ORR was 52.0% and CR rate was 31.5%. Median durations of response and CR were 10.2 and 17.9 months, respectively. Undetectable minimal residual disease at cycle 4 day 15 was associated with PFS benefit. With a step-up of 0.7 to 4 to 20 mg (n = 60), CRS was the most common treatment-emergent adverse event (53.3% (grade ≥3, 1.7%)). No immune effector cell-associated neurotoxicity syndrome was reported. Infections were reported in 82/127 (64.6%) patients (grade ≥3, 38.6%; coronavirus disease 2019, 18.1% (grade ≥3, 12.6%)). In conclusion, odronextamab showed encouraging efficacy in heavily pretreated R/R DLBCL and generally manageable safety with supportive care. Clinical trial registration: NCT03888105 .

Nature CancerVol. 6(3)
Ulsan College (KR), University of Modena and Reggio Emilia (IT), Universitat Autònoma de Barcelona (ES), Università degli Studi del Piemonte Orientale “Amedeo Avogadro” (IT), University of Iowa (US), Atrium Health Wake Forest Baptist (US), Rush University Medical Center (US), Tufts Medical Center (US), Dalhousie University (CA), Tokai University (JP), Beth Israel Deaconess Medical Center (US), Cleveland Clinic (US), Ewha Womans University (KR), University of Alberta (CA), Harbin Medical University (CN), Sun Yat-sen University (CN), The University of Melbourne (AU), China Medical University (TW), Regeneron (United States) (US), Yonsei University (KR), Jilin University (CN), Korea University (KR), Chinese Academy of Medical Sciences & Peking Union Medical College (CN), Peking University (CN), Norton Healthcare (US), Cornell University (US), Singapore General Hospital (SG), Sichuan University (CN), Fudan University (CN), University of Michigan (US), Japanese Red Cross Society, Japan (JP), Geelong Hospital (AU), Royal Cornwall Hospital (GB), Epworth Hospital (AU), University Hospital of Wales (GB), Dong-A University Hospital (KR), Stony Brook University Hospital (US), Ospedale di Circolo e Fondazione Macchi (IT), Hospital de Sant Pau (ES), Samsung Medical Center (KR), University of Iowa Hospitals and Clinics (US), Tianjin Medical University Cancer Institute and Hospital (CN), Hudson Institute of Medical Research (AU), Derriford Hospital (GB), Seoul National University Hospital (KR), Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (IT), Centre Hospitalier Universitaire de Bordeaux (FR), Centre Hospitalier Universitaire de Lille (FR), Hospital Universitari i Politècnic La Fe (ES), Centre Hospitalier Universitaire Henri-Mondor (FR), Wuhan University (CN), Wroclaw Medical University (PL), Soochow University (CN), Sorbonne Université (FR), University of Ulsan (KR), Kyoto Prefectural University of Medicine (JP), Institut d'Investigació Biomédica de Bellvitge (ES), Azienda Ospedaliera di Perugia (IT), West China Hospital of Sichuan University (CN), Azienda Sanitaria Unità Locale di Reggio Emilia (IT), Instytut Hematologii i Transfuzjologi (PL), Ospedale "Santa Maria delle Croci" di Ravenna (IT), Fudan University Shanghai Cancer Center (CN), National Hospital Organization Kyushu Cancer Center (JP), Kaohsiung Chang Gung Memorial Hospital (TW), Peking University Cancer Hospital (CN), Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda (IT), Azienda Ospedaliera San Camillo-Forlanini (IT), Assistance Publique – Hôpitaux de Paris (FR), Complejo Hospitalario de Salamanca (ES), Hospices Civils de Lyon (FR), Hospital Universitario 12 De Octubre (ES), National University Cancer Institute, Singapore (SG), Third Affiliated Hospital of Harbin Medical University (CN), Institut Català d'Oncologia (ES), Hospital Universitario Quirónsalud Madrid (ES), Copernicus Memorial Hospital (PL), Centre Hospitalier Universitaire de Poitiers (FR), Hospital Clínic de Barcelona (ES), Chiba Cancer Center (JP), Istituto di Ematologia di Bologna (IT), Michigan Center for Translational Pathology (US), National Cancer Center (KR), Royal Marsden Hospital (GB), Pitié-Salpêtrière Hospital (FR), First Affiliated Hospital of Xi'an Jiaotong University (CN), Medical University of Lodz (PL), Mayo Clinic in Arizona (US), First Hospital of Jilin University (CN), Health Research Institute of the Balearic Islands (ES), Universitätsklinikum Würzburg (DE), China Medical University Hospital (TW), Zhongshan Hospital (CN), Keimyung University Dongsan Medical Center (KR), The First Affiliated Hospital, Sun Yat-sen University (CN), Hospital Universitario Fundación Jiménez Díaz (ES), Oklahoma State University Oklahoma City (US), National Taiwan University Hospital (TW), Saitama International Medical Center (JP), Ulsan University Hospital (KR), Koo Foundation Sun Yat-Sen Cancer Center (TW), National Cancer Centre Singapore (SG), Schwarzwald-Baar Klinikum (DE), National Hospital Organization (JP), Hospital Universitario HM Sanchinarro (ES), Renmin Hospital of Wuhan University (CN), Shikoku Cancer Center (JP), Peking University Third Hospital (CN), Hôpital Saint-Louis (FR), Ospedale dell' Angelo (IT), National Cancer Center Hospital East (JP), National University Hospital (SG), Sun Yat-sen University Cancer Center (CN), Institute of Hematology & Blood Diseases Hospital (CN), Hackensack Meridian Health (US), Nagoya Medical Center (JP), Hospital Universitario Son Espases (ES), Istituti di Ricovero e Cura a Carattere Scientifico (IT), Japanese Red Cross Nagoya Daini Hospital (JP), King's College Hospital (GB), First Affiliated Hospital of Soochow University (CN), Hôpital Claude Huriez (FR), Azienda Usl Toscana Centro (IT), First Affiliated Hospital of Zhengzhou University (CN), Second Affiliated Hospital of Zhejiang University (CN), Centro de Investigación Biomédica en Red de Cáncer (ES), National Cheng Kung University Hospital (TW), The Catholic University of Korea Seoul St. Mary's Hospital (KR), Tongji Hospital (CN), Kobe City Medical Center General Hospital (JP), Austin Health (AU), Yamagata University Hospital (JP), Osaka City University Hospital (JP), First Affiliated Hospital Zhejiang University (CN), Japanese Foundation For Cancer Research (JP), Osaka Metropolitan University (JP), Weill Cornell Medicine (US), OU Health Stephenson Cancer Center, Aziende Socio Sanitarie Territoriale dei Sette Laghi, Huazhong University of Science and Technology (CN), Keimyung University (KR), Martin Luther University Halle-Wittenberg (DE), Universitat de Barcelona (ES), Gdańsk Medical University (PL), Sungkyunkwan University (KR), Saitama Medical University (JP), The University of Texas Southwestern Medical Center (US), Catholic University of Korea (KR), University of Bologna (IT), Nantes Université (FR), Université de Caen Normandie (FR)
Regeneron Pharmaceuticals
Good health and well-being
Openalex Percentile: Top 0%
CAR-T cell therapy research
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