Glofitamab Combo Boosts Survival vs Rituximab in Relapsed/Refractory DLBCL

Efficacy data from the trial revealed that after a median follow-up of 24.7 months, glofitamab plus GemOx exhibited superior OS vs rituximab/GemOx; the median OS was not evaluable vs 13.5 months in respective groups.

Glofitamab (Columvi) plus chemotherapy with gemcitabine and oxaliplatin (GemOx) showed enhanced progression-free survival (PFS) and overall survival (OS) outcomes vs rituximab (Rituxan) plus GemOx in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), according to a 2-year follow-up analysis of the phase 3 STARGLO trial (NCT04408638) presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting.

Efficacy data from the trial revealed that after a median follow-up of 24.7 months, glofitamab plus GemOx exhibited superior OS vs rituximab/GemOx; the median OS was not evaluable (NE; 95% CI, 19.2-NE) vs 13.5 months (95% CI, 7.9-18.5; HR, 0.60; 95% CI, 0.42-0.85; P = .003). Additionally, the 24-month OS rate in each arm was 54.4% (95% CI, 46.8%-62.0%) vs 33.6% (95% CI, 22.9%-44.2%). The median PFS in each arm was 13.8 months (95% CI, 8.8-30.0) vs 3.6 months (95% CI, 2.5-7.1), with respective 18-month PFS rates of 46.5% (95% CI, 38.5%-54.5%) vs 23.0% (95% CI, 11.5%-34.4%).

The objective response rates (ORRs) in the glofitamab and rituximab arms were 68.3% (95% CI, 61.0%-75.0%) vs 40.7% (95% CI, 30.5%-51.5%). Furthermore, the complete response (CR) rate with glofitamab was 58.5% (95% CI, 51.0%-65.7%) vs 25.3% (95% CI, 16.8%-35.5%) with rituximab. Among responders to glofitamab, the median duration of CR was not reached (NR; 95% CI, 27.2-NE) vs 24.2 months (95% CI, 6.9-NE) for responders to rituximab. A total of 42.1% of the glofitamab arm and 17.6% of the rituximab arm had an ongoing CR at data cut-off.

Following the end of treatment, the median OS and PFS was NE in the glofitamab arm. The respective 12-month OS and PFS rates were 89.3% (95% CI, 82.3%-96.4%) and 82.4% (95% CI, 72.2%-92.5%).

“With 2-year follow-up data of the [phase 3] STARGLO trial, glofitamab/GemOx continues to show a sustained benefit in OS, PFS, and response compared to [rituximab]/GemOx,” Jeremy S. Abramson, MD, director of the Jon and Jo Ann Hagler Center for Lymphoma at the Massachusetts General Hospital and a professor of Medicine at Harvard Medical School, said in the presentation. “We saw that more than half of patients remain alive after glofitamab/GemOx, and the majority of responders were not only alive, but progression-free.”

Patients in the phase 3 trial were randomly assigned 2:1 to receive glofitamab plus GemOx (n = 183) or rituximab plus GemOx (n = 91). Those in the glofitamab arm received step-up dosing in cycle 1, then a 30 mg target dose every 31 days starting cycle 2, day 1. Patients were given 8 cycles of glofitamab with GemOx followed by 4 cycles of glofitamab as monotherapy.

In the rituximab and glofitamab arms, respectively, the median age was 69.0 years (range, 20-84) vs 68.0 years (range, 22-88), 58.2% vs 57.4% of patients were male, and 56.0% vs 47.0% were Asian. A total of 62.6% vs 62.8% had 1 prior line of therapy, 51.6% vs 57.9% were primary refractory to last treatment, and 90.9% vs 88.9% had an ECOG performance status of 0 or 1. Furthermore, 77.8% vs 66.7% had Ann Arbor stage III or IV disease, 15.6% vs 12.6% had bulky disease of 10 cm or greater, and 8.8% vs 7.7% received prior CAR T-cell therapy.

The primary end point of the trial was OS. Secondary end points included independent review committee–assessed PFS and CR rates, with a landmark analysis of patients with CRs at end of treatment performed.

Among those treated with rituximab and glofitamab, 17.0% vs 52.3% experienced serious adverse effects (AEs). Furthermore, 40.9% vs 76.7% experienced grade 3 or higher AEs, including 4.5% vs 7.0% of the respective arms experiencing grade 5 AEs. AEs leading to treatment discontinuation occurred in 12.5% and 25.6% of the rituximab and glofitamab arms.

In the glofitamab arm, the incidence of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) was 44.8% and 2.3%, with respective grade 3/4 rates of 2.3% and 0.6%. Infections of any grade occurred in 29.5% and 55.2% of the rituximab and glofitamab arms, respectively, with 9.1% and 16.9% of patients experiencing grade 3/4 infections, and 3.4% vs 3.5% experiencing grade 5 infections.

Reference

Abramson JS, Ku M, Hertzberg M, et al. Glofitamab plus gemcitabine and oxaliplatin (Glofit-GemOx) in patients (pts) with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL): 2-year (yr) follow-up of STARGLO. J Clin Oncol. 2025;43(suppl 16):7015. doi:10.1200/JCO.2025.43.16_suppl.7015