Odronextamab plus chemo safe as DLBCL treatment, with promising efficacy

Combination treatment with the CD20×CD3 bispecific antibody odronextamab and chemotherapy is generally safe among previously untreated diffuse large B cell lymphoma (DLBCL) patients, without new safety signals, as shown by the results from part 1 of the phase III Olympia-3 study.

This simplified regimen also demonstrates “encouraging” preliminary results for efficacy, with a complete response (CR) rate of 100 percent for dose level (DL) 2, “suggesting that rituximab may not be required to achieve depth of response,” said lead study author Dr Jean-Marie Michot, Gustave Roussy, Villejuif, France. [ASH 2025, abstract 65]

Twenty-two patients with DLBCL (median age 66 years, 11 male) were enrolled in part 1A at data cutoff (5 May 2025) and treated with odronextamab and chemotherapy in 6 x 21-day cycles.

Odronextamab was administered intravenously, with weekly step-up dosing (0.7/4/20 mg) beginning on cycle 1 day 8. This was followed by full doses on cycle 2 (days 8 and 15), cycles 3‒4 (days 1, 8, and 15), and cycle 5 day 1), as well as two full doses on cycle 5 day 8 and cycle 6 (days 1 and 15).

Michot and colleagues examined the full doses of 80 mg (DL1) and 160 mg (DL2). The median duration of follow-up was 9.0 months for DL1 and 4.5 months for DL2.

Of the patients, 77.8 percent in the DL1 group and 92.3 percent in the DL2 group completed six cycles of induction, with median duration of treatment exposure of 18.1 weeks and 18.9 weeks, respectively. Fifteen patients (68.2 percent) completed treatment in part 1A following cycle 6 initiation.

Eighteen patients (DL1: n=6; DL2: n=12) were evaluable for dose-limiting toxicities (DLTs), which did not occur during the observation period. All 22 patients had at least one treatment-emergent adverse event (TEAE), of whom 17 experienced treatment interruption or delay (DL1: n=6; DL2: n=11) and two ceased treatment (DL1: myocardial infarction; DL2: septic shock).

Neutropenia was the most common TEAE (DL1: 77.8 percent; DL2: 84.6 percent; all grade ≥3), followed by cytokine release syndrome (CRS; DL1: 33.3 percent; DL2: 76.9 percent) and anaemia (DL1: 33.3 percent and DL2: 53.8 percent).

Among the patients, 66.7 percent in the DL1 group and 92.3 percent in the DL2 group had infections, with grade ≥3 infections occurring in 22.2 percent and 61.5 percent, respectively. All CRS events were either grade 1 (DL1: 11.1 percent; DL2: 69.2 percent) or 2 (DL1: 22.2 percent; DL2: 7.7 percent). Tumour lysis syndrome or immune effector cell-associated neurotoxicity syndrome events did not occur.

Efficacy

The objective response rate (ORR) was 77.8 percent (95 percent confidence interval [CI], 40.0‒97.2) for DL1, with a CR rate of 66.7 percent (95 percent 29.9‒92.5). For DL2, the ORR and CR rate were both 100 percent (95 percent CI, 75.3‒100).

The median duration of response in 20 evaluable patients was not reached for both DL1 (95 percent CI, 2.5‒NE) and DL2 (95 percent CI, 2.9‒NE) groups. Event-free probabilities at 6 months were 85.7 percent (95 percent CI, 3.4‒97.9) for DL1 and 90.0 percent (95 percent CI, 47.3‒98.5) for DL2.

Furthermore, “[s]erum 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,” Michot said. Cytokine and T-cell counts were similar between groups after the cycle 2 day 8 first full dose.

B-cell counts decreased during the first week of chemotherapy. Complete clearance was achieved after the first dose of the combination treatment.

“No B-cell recovery was observed ≤90 days after end of treatment,” Michot said. “Baseline CD20 status and on-treatment ctDNA clearance will be presented.”