Jean-Marie Michot, MD, Institut Gustave Roussy, France, discusses results from Part 1A (dose escalation) of the OLYMPIA-3 study of odronextamab plus chemotherapy in patients with diffuse large B-cell lymphoma (DLBCL).
DLBCL is a form of non-Hodgkin lymphoma. Lymphomas occur when cells of the immune system, B lymphocytes, grow and multiply uncontrollably. DLBCL occurs mostly in adults and is aggressive. It can start in the lymph nodes or outside of the lymphatic system in the gastrointestinal tract, testes, thyroid, skin, breast, bone, or brain. Often, the first sign of DLBCL is a painless rapid swelling in the neck, armpit, abdomen, or groin caused by enlarged lymph nodes. Other symptoms include night sweats, unexplained fevers, and weight loss.
OLYMPIA-3 (NCT06091865) is a Phase 3, randomized, open-label, multicenter study, investigating whether Odronextamab + chemotherapy is superior to standard-of-care rituximab + chemotherapy in patients with previously untreated DLBCL (Part 2). The study consists of Part 1A (dose escalation) and Part 1B (dose optimization). Odronextamab is a CD20xCD3 bispecific antibody designed to bridge CD20 on cancer cells with CD3-expressing T cells to facilitate local T-cell activation and cancer-cell killing.
Recently, data from Part 1A was presented at the 2025 American Society of Hematology (ASH) Annual Meeting. Odronextamab doses of 80 mg (dose level 1 [DL1]) and 160 mg (DL2) were tested.
At the data cutoff of May 5, 2025, 22 patients with DLBCL were enrolled in Part 1A and were evaluable for safety and efficacy. The median duration of follow-up was 9 months for DL1 and 4.5 months for DL2. In the DL1 and DL2 groups, 77.8% and 92.3% of patients completed 6 cycles of induction, with median durations of treatment exposure of 18.1 weeks and 18.9 weeks, respectively. 68.2% were considered to have completed treatment in Part 1A following initiation dose-limiting toxicities (DLTs) were evaluable in 18 patients.
No patients experienced a DLT during the observation period. All 22 patients experienced one or more treatment-emergent adverse events, which led to treatment interruption/delay in 17 patients and to treatment discontinuation in two patients. The most common adverse events were neutropenia, cytokine release syndrome, and anemia. Grade 3 or greater adverse events occurred in all patients, with neutropenia being the most common. Additionally, infections occurred in 66.7% of patients at DL1 and 92.3% of patients at DL2.
For DL1, overall response rate was 77.8%, with a complete response rate of 66.7%. For Dl2, the overall response rate and complete response rate were both 100%. Among 20 evaluable patients, median duration of response was not reached for both DL1 and DL2, with six-month event-free probabilities of 85.7% and 90%.
Serum cytokines IL-6, IL-8, IFNγ, and TNFα were elevated with the first odronextamab-chemotherapy doses only, and T-cell margination was similar to that previously reported with odronextamab monotherapy. After the C2D8 first full dose, cytokine and T-cell counts were comparable between DL1 and DL2. B-cell counts decreased during week 1 of chemotherapy treatment and cleared completely after the first dose of odronextamab-chemotherapy. No B-cell recovery was observed on or before 90 days after end of treatment.
For more information, click here.
To learn more about DLBCL and other rare hematologic conditions, visit https://checkrare.com/diseases/hematologic-disorders/