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

Patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) progressing after chimeric antigen receptor T-cell therapy (CAR T) 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 T. Sixty patients received IV odronextamab weekly for 4 cycles followed by maintenance until progression. The primary endpoint 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 T, and 48.3% relapsed within 90 days of CAR T. 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. 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 months 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%), two of which were COVID-19. Odronextamab monotherapy demonstrated encouraging efficacy and generally manageable safety, supporting its potential as an off-the-shelf option for post-CAR T patients. This trial was registered at www.clinicaltrials.gov as #NCT02290951.