A recent phase 1 study, ELM-1, has demonstrated promising results for odronextamab, a CD20 x CD3 bispecific antibody, in treating patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) who experienced disease progression after CAR T-cell therapy. The primary analysis of the study, published in Blood and presented at the 2024 ASH Annual Meeting, revealed that odronextamab produced durable responses and had a manageable safety profile. With a median follow-up of 16.2 months, the overall response rate was 48.3%, including a complete response rate of 31.7%. Common adverse effects included cytokine release syndrome, but no severe cases were reported.

Potential Breakthrough in Post-CAR T Therapy Treatment

The introduction of odronextamab represents a significant advancement for patients who have relapsed following CAR T-cell therapy. This bispecific antibody offers a new therapeutic option with substantial efficacy and manageable side effects. In the study, nearly half of the participants achieved a positive response, indicating its potential to address an unmet medical need. Patients achieving complete responses showed excellent and lasting outcomes, suggesting a promising role in post-relapse treatment strategies.

The ELM-1 trial enrolled patients aged 18 and older with relapsed or refractory DLBCL who had undergone at least two prior lines of systemic therapy. Participants received odronextamab through a step-up dosing regimen, starting from 1/20 mg to 0.7/4/20 mg during the first cycle, escalating to 160 mg on days 1, 8, and 15 of subsequent cycles. Those achieving a sustained complete response transitioned to a maintenance dose. The study's primary endpoint was the overall response rate, while secondary endpoints included duration of response, complete response rate, and safety outcomes. Notably, odronextamab showed efficacy across various CAR T-cell products and regardless of the time to relapse post-CAR T therapy.

Managing Safety and Efficacy Challenges

While odronextamab demonstrated notable efficacy, managing its safety profile is crucial for its clinical application. The most common adverse effect was cytokine release syndrome, affecting nearly half of the patients, though none experienced severe cases. No instances of immune effector cell-associated neurotoxicity syndrome were observed. Infectious complications, as expected in this patient population, occurred in half of the participants, with more serious infections noted in 20% of cases. Two patients discontinued treatment due to infections, highlighting the importance of monitoring and mitigating infectious risks.

The study also evaluated the durability of responses, revealing a median duration of response of 14.8 months. Median progression-free survival was 4.8 months, and overall survival was 10.2 months. These findings underscore the potential of odronextamab as a viable treatment option for patients who have not been cured by CAR T-cell therapy. The ongoing understanding and management of infectious risks remain critical for optimizing the use of this bispecific antibody in clinical practice.