According to a primary analysis from the ELM-1 study, CD20-CD3 bispecific antibody odronextamab demonstrated encouraging efficacy and manageable safety among patients with relapsed/refractory DLBCL progressing after CAR T-cell therapy.

These results were presented by Matthew Matasar, MD, MS, Division of Blood Disorders, Rutgers Cancer Institute and RWJBarnabas Health, New Brunswick, New Jersey, at the 66^th ASH Annual Meeting in San Diego, California.

“Odronextamab monotherapy was associated with encouraging efficacy and generally manageable safety in a setting with limited treatment options and historically dismal outcomes,” wrote Matasar and colleagues.

“Efficacy was observed even in patients relapsing in ≤90 days, supporting the potential of odronextamab as an accessible, off-the-shelf option in the post-CAR-T setting,” they added.

Transcript:

Hi, I'm Dr Matthew Matasar from the Rutgers Cancer Institute and I'm here at the 66th session of ASH and I'm proud to share with you some of our findings from the ELM-1 study, specifically our cohort of 60 patients that we treated with odronextamab monotherapy after prior treatment and failure of CAR T-cell therapy.

We know that CAR T-cell therapy has changed the landscape for relapsed large cell lymphoma, but only approximately one third of patients will be cured by such treatment and treatments subsequent to CAR T really represent a major unmet need, prognosis remains poor after relapse following CAR T-cell therapy.

Odronextamab does have activity in the setting as we found in ELM-1, in the 60 patients that we treated we found an overall response rate of 48% and complete response rate of 32%. Especially for patients that achieve a complete response to odronextamab, the durability can be quite impressive, and we have a median follow-up of 16 months, the median complete response has not yet been reached in these patients. Not everybody does respond and there clearly is a relationship between the durability of response to the prior CAR T-cell therapy and the likelihood of response to odronextamab.

For patients that are relapsing 6 months or longer after CAR T-cell therapy, activity is excellent with an overall response rate north of 80%, complete response rates of 50 to 70%. Whereas patients that are relapsing within three months of CAR T-cell therapy have a worse prognosis and a lower response to odronextamab with an overall response rate of only 20% and the complete response rate of only 10%.

In terms of safety we found that this treatment is safe in this context. Approximately half of patients experience cytokine release of any grade, but this was restricted only to grade 1 and grade 2, was short in duration, and resolved with usual supportive measures. There were no grade 5 CRS events and ICANS occurred during the course of this study. There were infectious complications that we saw, which should not be surprising given prior CAR and given that we know that the bispecific targeting CD20 themselves do confer infectious risks.

Overall though, I would say that we found that odronextamab monotherapy post-CAR is safe and effective and really may represent an opportunity going forward to offer patients relapsing after CAR another chance at response.
 

Source:

Matasar M, Topp S, Allan J, et al. Efficacy and Safety of Odronextamab Monotherapy in Patients (Pts) with Diffuse Large B-Cell Lymphoma (DLBCL) Progressing after CAR T-Cell Therapy: Primary Analysis from the ELM-1 Study. Presented at the 66^th ASH Annual Meeting & Exposition; December 7-10, 2024; San Diego, California. Abstract 866.