Odronextamab (Ordspono) has demonstrated a manageable safety profile in patients with diffuse large B-cell lymphoma (DLBCL) who have progressed after CAR T-cell therapy, according to findings from the ELM-1 study (NCT02290951). The study, evaluating odronextamab monotherapy, was presented at the 2024 American Society of Hematology Annual Meeting & Exposition (ASH). The results suggest that odronextamab could offer a valuable treatment option for this challenging patient population.
Safety Profile
According to Dr. Matthew J. Matasar, chief of the Division of Blood Disorders at Rutgers Cancer Institute, treatment with odronextamab was generally safe. The most common treatment-emergent adverse event was cytokine release syndrome (CRS), with 25.0% of patients experiencing a grade 1 event and 23.3% experiencing a grade 2 event. Importantly, no patients experienced a grade 3 or higher CRS event. There were no cases of immune-effector cell-associated neurotoxicity syndrome (ICANS) reported.
"In terms of safety, we found that odronextamab is safe in this patient population," said Dr. Matasar. "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."
Infectious Complications
Infectious complications were observed following treatment with odronextamab, which was anticipated in this patient population that had previously undergone CAR T-cell therapy. Grade 3 or greater infection rate was 20%. A retrospective analysis of the ELM-1 study sought to identify patients at a heightened risk for infectious complications using the CAR-HEMATOTOX model. The analysis indicated that patients with higher CAR-HEMATOTOX scores at baseline were at the greatest risk of infectious complications, suggesting a need for heightened surveillance or prophylaxis in these individuals.
"We know that bispecifics in general do have immunosuppressive qualities, so we continue to understand that management and mitigation of infectious risks is important," Dr. Matasar explained. "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."
Efficacy and Durability
While the primary focus of the reported findings was safety, Dr. Matasar noted that approximately half of the patients responded to odronextamab. Furthermore, patients who achieved a complete response (CR) experienced excellent, endurable responses, suggesting a potential role for odronextamab in treating patients after relapse following CAR T-cell therapy.
In total, 5 patients discontinued odronextamab due to treatment-related AEs, and 1 treatment-related death occurred due to COVID-19 pneumonia. No cases of tumor flare or tumor lysis syndrome were observed.
