Dr Luminari on the Safety Profile of Odronextamab in Relapsed/Refractory Follicular Lymphoma

“Treatment discontinuation [of odronextamab in patients with relapsed/refractory follicular lymphoma] was mostly due to infection and COVID-19 infections. There were 5 [reported] cases [of] treatment-related adverse effects, which caused the death of [8] patients.”

Stefano Luminari, MD, an associate professor of Oncology at the University of Modena and Reggio Emilia, detailed the safety profile of odronextamab (REGN1979) for the treatment of patients with relapsed/refractory follicular lymphoma.

Two-year follow-up safety data from the phase 2 ELM-2 study (NCT03888105), presented at the 2025 EHA Congress, demonstrated that the safety profile of odronextamab was similar to previously published data, without any new safety signals, Luminari began. However, he noted that the most common any-grade adverse effect (AE) was cytokine release syndrome (CRS). Specifically, patients who received the 0.7/4/20-mg dosing regimen (n = 60) experienced any-grade CRS at a rate of 56.7%, comprising grade 1 (45.0%), grade 2 (10.0%), and grade 3 (1.7%) CRS. Of note, the median time to CRS onset was 19.67 hours (range, 0.7-159.0), and the median CRS duration was 7.72 hours (range, 0.6-184.0). Other than CRS, the most common treatment-emergent AEs (TEAEs) observed in at least 15% of patients in the overall population (n = 128) included neutropenia (39.8%), pyrexia (38.3%), anemia (34.4%), and COVID-19 (32.8%), Luminari stated. The most common TEAE leading to treatment discontinuation was COVID-19 (3.1%), Luminari concluded.

Additionally, the most common treatment-related TEAEs leading to treatment discontinuation included infusion-related reactions (2.3%) and pneumonia (1.6%). Treatment-related TRAEs that led to death included progressive multifocal leukoencephalopathy, pneumonia, pseudomonal pneumonia, and sepsis (n = 1 each), along with COVID-19–related pneumonia and systemic mycosis (n = 1 each).

In March 2024, the FDA issued a complete response letter to the biologics license application (BLA) seeking the approval of odronextamab for the treatment of patients with relapsed/refractory follicular lymphoma and relapsed/refractory diffuse large B-cell lymphoma (DLBCL), which was related to the enrollment status in confirmatory trials further evaluating the respective bispecific antibody. The FDA has since accepted a resubmission of the BLA for odronextamab for the same indication in February 2025. Moreover, in August 2024, the European Commission approved odronextamab for the treatment of patients with relapsed/refractory follicular lymphoma or DLBCL after at least 2 prior lines of systemic therapy.