Odronextamab Demonstrates Safety in Treating DLBCL Population

Odronextamab (Ordspono) displayed a manageable safety profile, eliciting primarily grade 1 or 2 instances of cytokine release syndrome (CRS) as well as no immune-effector cell-associated neurotoxicity syndrome (ICANS) cases, according to Matthew J. Matasar, MD.

CancerNetwork® spoke with Matasar, chief of the Division of Blood Disorders at Rutgers Cancer Institute and a professor of Medicine at Rutgers Robert Wood Johnson Medical School, about common toxicities associated with odronextamab, as well as how clinicians can best mitigate them. Matasar presented findings from the ELM-1 study (NCT02290951) evaluating odronextamab monotherapy in patients with diffuse large B-cell lymphoma (DLBCL) at the 2024 American Society of Hematology Annual Meeting & Exposition (ASH).1

Matasar stated that treatment with odronextamab was safe in patients with DLBCL, citing primarily low-grade CRS in approximately half of evaluable patients, with no grade 5 CRS instances reported. Furthermore, he expressed that infectious complications occurred following treatment with odronextamab, which he said was expected after prior CAR T-cell therapy.

Matasar highlighted an additional ASH presentation, a retrospective analysis of the ELM-1 study, which sought to identify patients at a heightened risk for infectious complications from the investigational agent by utilizing the CAR-HEMATOTOX model.2 He stated that patients with higher CAR-HEMATOTOX scores at baseline were at the greatest risk of infectious complications, warranting heightened observance or prophylaxis.

Findings from the primary analysis of the ELM-1 study reveal that the most common treatment-emergent adverse event was CRS, including 25.0% of patients experiencing a grade 1 event, 23.3% experiencing a grade 2 event, and no patients experiencing a grade 3 or higher event. Grade 3 or higher TEAEs occurred in 76.7% of evaluable patients.

In total, 5 patients discontinued odronextamab due to treatment-related AEs, and 1 treatment-related death occurred due to COVID-19 pneumonia. Furthermore, grade 3 or greater infection rate was 20%, and no cases of tumor flare or tumor lysis syndrome were observed.

Transcript:

In terms of safety, we found that odronextamab is safe in this patient population. Cytokine release syndrome [CRS] did occur in approximately half of the patients, but this was exclusively grade 1 or grade 2 in severity and was self-limited and effectively treated with usual supportive measures. There was no grade 5 CRS, and there was no immune-effector cell-associated neurotoxicity syndrome [ICANS] that occurred in the study. There were infectious complications, as would be expected in this patient population [post–CAR T-cell therapy].

We know that bispecifics in general do have immunosuppressive qualities, so we continue to understand that management and mitigation of infectious risks is important. To that end, we do have a sister presentation here at ASH looking at the use of the CAR-HEMATOTOX model to identify patients who are at heightened risk for infectious complications from odronextamab therapy. [We] found that patients with a high CAR-HEMATOTOX score at baseline are at the highest risk of infectious complications and may benefit from heightened surveillance or prophylaxis.

In summary, we found that odronextamab is safe and effective post–CAR T-cell therapy, with approximately half of the patients responding. Patients who achieve a complete response [CR] can have excellent, endurable responses, suggesting that [odronextamab] does potentially have a future role in [treating] patients after relapse following CAR T-cell therapy.

References

1. Matasar M, Topp MS, Allan JN, 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. Blood. 2024;144(suppl 1):866. doi:10.1182/blood-2024-199155
2. Matasar M, Tucker D, Kim TM, et al. Evaluation of CAR-Hematotox scoring as a predictor of infection risk following treatment with odronextamab (a CD20×CD3 bispecific antibody) in relapsed/refractory diffuse large B-Cell lymphoma. Blood. 2024;144(suppl 1):3076. doi:10.1182/blood-2024-200259