Glofitamab plus gemcitabine/oxaliplatin in relapsed/refractory diffuse large B-cell lymphoma: Phase III STARGLO trial 3-year follow-up.

Abstract

Background: Glofitamab plus gemcitabine/oxaliplatin (Glofit-GemOx) has demonstrated significant improvements in overall survival (OS), progression-free survival (PFS) and complete response (CR) rate in autologous stem cell transplant (ASCT)-ineligible patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL). We report 3-year follow-up efficacy and safety results for Glofit-GemOx versus rituximab (R)-GemOx in patients with R/R DLBCL after >=1 prior therapy (PT) in the Phase III STARGLO trial (NCT04408638). Method(s): Patients were randomised 2:1 to Glofit-GemOx (8 cycles [C] + 4C glofitamab monotherapy) or R-GemOx (8C) and stratified by PT (1 vs. >=2) and refractoriness to last therapy. Following obinutuzumab pretreatment, glofitamab was given as weekly step-up doses (2.5/10 mg) in C1, then 30 mg every 21days from C2. Patients with 1PT had to be ASCT-ineligible. Primary endpoint was OS. Key secondary endpoints included independent review committee-assessed PFS and CR rate. Landmark analyses of patients with CR at end of treatment (EOT) were conducted. Result(s): 274 patients with R/R DLBCL were enrolled (Glofit-GemOx/R-GemOx, n = 183/91; intent-to-treat [ITT]). 172 (62.8%) had 1PT; 153 (55.8%) had primary refractory disease; 166 (60.6%) were refractory to last therapy. Of those with 1PT, 95 (55.2%) were primary refractory. As of 01/05/2025 (median follow-up: 35.1 months [m]), Glofit-GemOx demonstrated favourable outcomes versus R-GemOx (ITT): median OS, 25.5 m versus 12.5 m (hazard ratio [HR]:0.60, 95% confidence interval [CI]:0.43-0.83); median PFS, 14.4 m versus 3.3 m (0.41, 0.29-0.57); CR rate, 58.5% versus 25.3%. 36-month OS estimates were 47.1%/27.4% for Glofit-GemOx/R-GemOx; 30-month PFS estimates were 38.1%/15.2%. Amongst Glofit-GemOxtreated patients with CR at EOT, 24-month OS/PFS rates were 79.4%/74.2%. Benefit was observed with Glofit-GemOx versus R-GemOx in patients with 1PT: median OS, not estimable versus 14.4 m (HR: 0.58, 95%CI:0.38-0.89); median PFS, 20.4 m versus 5.5 m (0.49, 0.31-0.78); CR rate, 63.5% versus 28.1%. 36-month OS estimates for these patients were 54.6%/30.8% for Glofit-GemOx/R-GemOx; 30-month PFS estimates were 41.5%/26.3%. No new safety signals, cumulative toxicity or new long-term adverse events were identified. Immune recovery was observed, with median B-cell and immunoglobulin M counts above lower limit of normal 18-24 m after EOT. Glofit-GemOx did not negatively affect T-cell levels. Conclusion(s): Superior OS, PFS and CR rates in ASCT-ineligible patients with R/R DLBCL, and benefit for those with 1PT, were observed with Glofit-GemOx versus R-GemOx at 3-year follow-up. Most patients reaching CR remained progression-free and alive (74.2%) 2 years after EOT. Fixed-duration Glofit-GemOx demonstrated high CR rate, sustained remission and continued survival advantages in DLBCL.