As reported in The Lancet by Abramson et al, the phase III STARGLO trial has shown significantly improved overall survival with glofitamab plus gemcitabine/oxaliplatin vs rituximab plus gemcitabine/oxaliplatin in patients with transplant-ineligible relapsed or refractory diffuse large B-cell lymphoma.

Study Details

In the open-label trial, 274 patients (median age = 68 years) with at least one prior line of therapy from sites in 13 countries in Asia, Australia, Europe, and North America were randomly assigned 2:1 between February 2021 and March 2023 to receive glofitamab plus gemcitabine/oxaliplatin (n = 183) rituximab plus gemcitabine/oxaliplatin (n = 91). Gemcitabine/oxaliplatin in both groups consisted of gemcitabine at 1,000 mg/m² and oxaliplatin at 100 mg/m² on day 2 of cycle 1 and then day 1 of subsequent cycles for up to eight 21-day cycles. Rituximab at 375 mg/m² was given at day 1 of each cycle for up to eight cycles. Glofitamab was given in step-up dosing during cycle 1 and then 30 mg on day 1 of cycles 2 to 8 and for four additional cycles of monotherapy. The primary endpoint was overall survival.

Overall Survival

At primary analysis after median follow-up of 11.3 months (95% confidence interval [CI] = 9.6–12.7 months), median overall survival was not estimable (95% CI = 13.8 months to not estimable) in the glofitamab combination group vs 9.0 months (95% CI = 7.3–14.4 months) in the rituximab combination group (hazard ratio [HR] = 0.59, 95% CI = 0.40–0.89, P = .011).

In an updated analysis after median follow-up of 20.7 months (95% CI = 19.9–23.3 months), median overall survival was 25.5 months (95% CI = 18.3 months to not evaluable) in the glofitamab combination group vs 12.9 months (95% CI = 7.9–18.5 months) in the rituximab combination group (HR = 0.62, 95% CI = 0.43–0.88).

Adverse Events

Grade ≥ 3 adverse events occurred in 78% of the glofitamab combination group and 41% of the rituximab combination group. Serious adverse events occurred in 54% vs 17%. Adverse events led to discontinuation of any study drug in 27% vs 13% of patients. Cytokine-release syndrome occurred in 44% of the patients who received the glofitamab combination group and was grade 3 in 2%; any-grade immune effector cell–associated neurotoxicity syndrome occurred in 2% and was grade 3 in 1%. Adverse events led to death in 8% vs 5% of patients, with death attributable to glofitamab occurring in five patients (3%) and death attributable to rituximab occurring in one patient (1%).

The investigators concluded: “[Glofitamab plus gemcitabine/oxaliplatin] had a significant overall survival benefit compared with [rituximab plus gemcitabine/oxaliplatin], supporting its use in transplant-ineligible patients with relapsed or refractory diffuse large B-cell lymphoma after one or more previous lines of therapy.”

Jeremy S. Abramson, MD, of Massachusetts General Hospital Cancer Center, is the corresponding author of The Lancet article.

Disclosure: The study was funded by F. Hoffmann–La Roche. For full disclosures of the study authors, visit www.thelancet.com.