Odronextamab, a bispecific antibody, is showing promise in treating patients with diffuse large B-cell lymphoma (DLBCL) who have relapsed after CAR T-cell therapy. Data from the ELM-1 study (NCT02290951), presented at the 2024 American Society of Hematology Annual Meeting & Exposition (ASH), indicate that the duration of benefit from prior CAR T-cell therapy significantly impacts the likelihood of response to odronextamab.
Impact of Prior CAR T-Cell Therapy Duration
Matthew J. Matasar, MD, chief of the Division of Blood Disorders at Rutgers Cancer Institute, emphasized the importance of identifying patient subgroups that can benefit from odronextamab after CAR T-cell therapy. The ELM-1 study revealed a correlation between the duration of response to prior CAR T-cell therapy and the efficacy of odronextamab. Patients who relapsed more than six months after CAR T-cell therapy showed significantly better responses to odronextamab.
ELM-1 Study Efficacy Findings
The primary analysis of the ELM-1 study demonstrated an overall response rate (ORR) of 48.3% (95% CI, 35.2%-61.6%) and a complete response (CR) rate of 31.7% (95% CI, 20.3%-45.0%) by independent central review. Notably, patients who relapsed within 90 days of CAR T-cell therapy had an ORR of 20.7% (95% CI, 8.0%-39.7%), while those relapsing between 91 and 180 days had an ORR of 63.6% (95% CI, 30.8%-89.1%). The median duration of response was 14.8 months (95% CI, 2.8-NE), and the median progression-free survival and overall survival were 4.8 months (95% CI, 2.6-5.4) and 10.2 months (95% CI, 4.6-15.8), respectively.
Addressing CAR T-Cell Therapy Failure
With the increasing use of CAR T-cell therapy, there is a growing need for effective treatments for patients who relapse or do not respond to this therapy. Dr. Matasar highlighted the necessity of developing programs to address this unmet need, suggesting that bispecific antibodies like odronextamab may offer a solution. Combination approaches utilizing odronextamab are being explored to potentially mitigate disease progression and improve outcomes following CAR T-cell therapy failure.
Future Directions
Ongoing research is focused on identifying optimal combination strategies with odronextamab to enhance its efficacy and potentially achieve curative potential in patients with DLBCL who have failed CAR T-cell therapy. The ELM-1 study provides valuable insights into the role of bispecific antibodies in this challenging clinical scenario, paving the way for improved treatment options.
