An updated analysis of outcomes in the ELM-1 trial from a pre-specified cohort of patients demonstrates that CD20-CD3 bispecific antibody odronextamab monotherapy demonstrated promising antitumor activity and manageable safety among heavily pretreated patients with diffuse large B-cell lymphoma (DLBCL) who have progressed after CAR T-cell therapy.

Jennifer L. Crombie, MD, Dana Farber Cancer Institute, Boston, MA, reported these updated data onsite at the 2023 American Society of Hematology (ASH) Annual Meeting in San Diego, CA.

The primary end point of the trial was overall response rate (ORR), which was assessed by Independent Central Review (ICR), according to the Lugano classification. Key secondary endpoints included duration of response (DoR), progression-free survival (PFS), and overall survival (OS). As of Dec 20, 2022, 46 patients were treated, with 44 patients evaluable for efficacy after 4.9 months median duration of follow-up. The ORR and complete response (CR) rate by ICR were 48% and 30%, respectively. It was noted that responses were durable, and both median DoR and median duration of CR were not reached. The probability of maintaining a response for 12 months was 62% and the probability of maintaining a CR for 9 months was 86%. 

Intravenous odronextamab was administered weekly in 21-day cycles during cycles 1 to 4. Odronextamab was administered with steroid prophylaxis and step-up doses of 0.7/4/20 mg during cycle 1 to mitigate the risk of cytokine release syndrome (CRS). This was followed by 160 mg on days 1, 8, and 15 of cycles 2 to 4. After cycle 4, odronextamab maintenance treatment continued at 320 mg every 2 weeks until disease progression or unacceptable toxicity. The patients who achieved a CR that was durable for ≥9 months transitioned to dosing with 320 mg every 4 weeks. 

Investigators determined that patients with DLBCL treated with CAR T who were evaluable for biomarker analysis had lower T-cell counts at baseline compared with CAR T naive DLBCL patients, yet the fold-change of T-cell expansion at C4D15 was greater in CAR T treated patients versus CAR T naive patients.

It was observed that 6 patients permanently discontinued odronextamab due to a treatment-emergent adverse events such as device-related infection, pneumonia, dysphagia, gait disturbance, leukemia, and encephalopathy. The most common treatment-emergent event was CRS (any grade, 52%). The highest grade of CRS reported was Grade 2, and low-grade CRS events occurred in 46% of patients with the 0.7/4/20 mg step-up regimen. No cases of immune effector cell-associated neurotoxicity syndrome (ICANS) were reported among patients with the 0.7/4/20 mg regimen. Grade ≥3 infections occurred in 10 patients, with no grade 5 events. Additionally, no cases of tumor flare were reported.

Dr Crombie and colleagues concluded, “Odronextamab monotherapy demonstrates encouraging antitumor activity in heavily pretreated [patients] who have progressed after CAR T therapy, with a generally manageable safety profile. Durable [complete responses] were achieved in this difficult-to-treat setting. These data support the potential role of odronextamab in the treatment paradigm for R/R DLBCL.” 

“Further studies to evaluate the optimal sequencing and combinations of odronextamab with CAR-T therapy are warranted,” they added. 

Source:

Crombie J, Matasar M, Topp M, et al. Odronextamab demonstrates durable complete responses in patients with diffuse large b-cell lymphoma (DLBCL) progressing after CAR-T therapy: Outcomes from the ELM-1 study. Presented at ASH Annual Meeting and Exposition; December 9-12, 2023; San Diego, CA. Abstract 4461