Abstract Background Glofitamab, a CD20xCD3 bispecific antibody, when combined with GemOx (Glofit-GemOx) has demonstrated significant improvements in overall survival (OS), progression-free survival (PFS), and complete response (CR) rate in patients with R/R DLBCL who are ineligible for autologous stem cell transplant (ASCT; Abramson et al. Lancet 2024). We report updated efficacy and safety of Glofit-GemOx versus R-GemOx, with 3 years of follow-up, in patients with R/R DLBCL after ≥1 prior line of therapy (LOT) from the global Phase III STARGLO trial (NCT04408638). Methods Patients were randomized 2:1 to either Glofit-GemOx (8 cycles plus 4 cycles glofitamab monotherapy) or R-GemOx (8 cycles) and stratified by number of prior LOT (1 vs ≥2) and refractoriness to last therapy. Following obinutuzumab pretreatment, glofitamab was given in Cycle 1 as weekly step-up doses (2.5/10mg), then 30mg target dose every 21 days from Cycle 2 Day 1. Patients enrolling after 1 prior LOT had to be ineligible for ASCT. The primary endpoint was OS. Secondary endpoints included independent review committee (IRC)-assessed PFS and CR rate. Landmark analyses of patients in CR at end of treatment (EOT) were conducted. Results Of the 274 (Glofit-GemOx, n=183; R-GemOx, n=91) patients with R/R DLBCL enrolled (intent-to-treat ITT population), 172 (62.8%) had 1 prior LOT, 102 (37.2%) had ≥2 prior LOT, 153 (55.8%) had primary refractory disease, and 166 (60.6%) were refractory to their last therapy. Of the patients with 1 prior LOT, 95 (55.2%) were primary refractory. Baseline characteristics were unchanged and balanced across arms. After 3 years of OS follow up (data cut-off: May 1, 2025; median follow-up: 35.1 months), Glofit-GemOx continued to demonstrate favorable outcomes versus R-GemOx in the ITT: median OS, 25.5 vs 12.5 months (hazard ratio HR 0.60, 95% confidence interval CI: 0.43–0.83); IRC-assessed median PFS, 14.4 vs 3.3 months (HR 0.41, 95% CI: 0.29–0.57); and CR rate, 58.5 vs 25.3%, respectively. The 36-month OS estimates were 47.1% for Glofit-GemOx and 27.4% for R-GemOx, and the 30-month PFS estimates were 38.1% for Glofit-GemOx and 15.2% for R-GemOx. Among patients who achieved CR at any time point (Glofit-GemOx, n=107; R-GemOx, n=23; median follow-up: 24.0 months), median duration of CR was not reached (95% CI: 27.2–not estimable NE) with Glofit-GemOx and was 24.2 months (95% CI: 6.9–NE) with R-GemOx. Amongst Glofit-GemOx-treated patients with a CR at EOT, the 24-month OS and PFS rates were 79.4% and 74.2%, respectively. A more pronounced efficacy benefit was observed for Glofit-GemOx versus R-GemOx in patients with 1 prior LOT: median OS, NE vs 14.4 months (HR 0.58, 95% CI: 0.38–0.89); median PFS, 20.4 vs 5.5 months (HR 0.49, 95% CI: 0.31–0.78); and CR rate (63.5 vs 28.1%). The 36-month OS estimates for these patients were 54.6% with Glofit-GemOx and 30.8% with R-GemOx, and the 30-month PFS estimates were 41.5% for Glofit-GemOx and 26.3 for R-GemOx. The safety profile was unchanged with extended follow up: no new signals were identified, and no evidence of cumulative toxicity or new long-term adverse events (AEs) were observed. In glofitamab-exposed patients, cytokine release syndrome (CRS) remained the most common AE (44.8%: Grade 1, 32.0%; Grade 2, 10.5%; Grade 3, 2.3%) and events consistent with immune effector cell-associated neurotoxicity syndrome occurred in 4 patients (all concurrent with CRS; most Grade 1–2 n=3). Infections and infestations occurred in 55.2% of glofitamab-exposed patients, with COVID-19 the most common infection (16.3%), occurring during the COVID-19 pandemic. Immune recovery was observed, with median B-cell and immunoglobulin M counts above the lower limit of normal 18–24 months after EOT. Glofit-GemOx treatment did not negatively affect T-cell levels. Conclusion After 3 years of follow-up, sustained benefits with Glofit-GemOx treatment were observed, demonstrating superior OS, PFS, and CR rates compared with R-GemOx in ASCT-ineligible patients with R/R DLBCL. Most patients that reached CR remained progression free and alive 2 years after EOT. A more pronounced efficacy benefit was observed for Glofit-GemOx versus R-GemOx in patients with 1 prior LOT. The safety profile remained consistent with the known risks of each study drug and was manageable. This updated analysis demonstrates the sustained remission and continued survival advantages that fixed-duration Glofit-GemOx offers for patients with R/R DLBCL.
Abramson et al. (Mon,) studied this question.
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