Odronextamab monotherapy in R/R DLBCL after progression with CAR T-cell therapy: primary analysis of the ELM-1 study
Abstract
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.
Article Details
Authors (19)
Max S. Topp
17Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg, Würzburg, Germany
Matthew Matasar
6Rutgers Cancer Institute, New Brunswick, United States
John N. Allan
3Division of Hematology and Medical Oncology, Weill Cornell Medicine, New York, NY
Stephen M. Ansell
3Department of Hematology/Oncology, Mayo School of Graduate Medicine, Mayo Clinic, Rochester, MN
Jeffrey A. Barnes
5Hematology and Oncology Division, Department of Medicine, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA
Jon E. Arnason
Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States
Jean-Marie Michot
15Gustave Roussy Institute of Cancer, Département d'Innovation Thérapeutique et d'Essais Précoces (DITEP), Villejuif, France
Neta Goldschmidt
3Department of Hematology, Hadassah Medical Center, Jerusalem, Israel
Susan M. O’Brien
9Division of Hematology/Oncology, Department of Medicine, Chao Family Comprehensive Cancer Center, University of California Irvine Medical Center, Orange, CA
Uri Abadi
12Meir Medical Center, Hematology, Kfar Saba, Israel
Irit Avivi
From Tel Aviv Sourasky Medical Center (Y.C.C., I.A.), and the Faculty of Medical and Health Sciences, Tel Aviv University (Y.C.C., H.M., I.A.), Tel Aviv, Chaim Sheba Medical Center, Ramat Gan (H.M.), and Hadassah Hebrew University Medical Center, Jerusalem (M.G.) — all in Israel; McGill University and McGill University Health Centre, Montreal (M.S.), and Alberta Health Services, Edmonton (M.P.C.) — all in Canada; Samsung Medical Center, Sungkyunkwan University School of Medicine (K.K.), Seoul St. Mary’s Hospital, Catholic University of Korea (C.-K.M.), and Seoul National University College of Medicine (S.-S.Y.) — all in Seoul, South Korea; Hospital Universitario Marqués de Valdecilla, Instituto de Investigación Sanitaria Valdecilla, Universidad de Cantabria, Santander (E.M.O.), Cancer Center Clínica Universidad de Navarra, Center for Applied Medical Research, Pamplona (P.R.-O.), Institut Català d’Oncologia, Josep Carreras Leukemia Research Institute, and the Hospital Germans Trias i Pujol, Barcelona (A.O.)...
Yuan Cheng
Monash Suzhou Research Institute, Monash University, SIP, Suzhou, China.
Dina M. Flink
13Regeneron Pharmaceuticals, Inc., Tarrytown, NY
Min Zhu
Jurriaan Brouwer-Visser
6Regeneron Pharmaceuticals, Inc., Tarrytown, United States
Aafia Chaudhry
6Regeneron Pharmaceuticals, Inc., Tarrytown, United States
Hesham Mohamed
6Regeneron Pharmaceuticals, Inc., Tarrytown, United States
Srikanth Ambati
Beam Therapeutics, Cambridge, MA
Jennifer L. Crombie
1Dana-Farber Cancer Institute, Boston, MA