Glofitamab plus gemcitabine and oxaliplatin (GemOx) vs rituximab (R)-GemOx in patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL): Efficacy and safety in patient subgroups

Abstract Background Glofitamab, a CD20xCD3 bispecific antibody, plus GemOx (Glofit-GemOx) has shown overall survival (OS), progression-free survival (PFS), and complete response (CR) rate benefits compared with R-GemOx, in patients (pts) with autologous stem cell transplant (ASCT)-ineligible R/R DLBCL in the Phase III STARGLO trial (NCT04408638; Abramson et al. Lancet 2024). We present efficacy and safety in clinically relevant subgroups from STARGLO. Methods:Pts were randomized 2:1 to Glofit-GemOx (8 cycles plus 4 cycles of glofitamab monotherapy) or R-GemOx (8 cycles). Glofitamab was given in Cycle (C)1 as weekly step-up doses (2.5/10mg), with the 30mg target dose every 21 days from C2 Day 1. Pts with one prior line of therapy (LOT; second-line 2L) needed to be ASCT-ineligible. Endpoints included OS, PFS, and CR rate. Results:At the data cut-off (May 1, 2025), 183 pts were enrolled to Glofit-GemOx and 91 to R-GemOx; 101 pts were aged 65 years (y; n=67 and n=34), 173 were aged ≥65y (n=116 and n=57), and 66 were aged ≥75y (n=46 and n=20), respectively. Overall, 172 (62.8%) pts had one prior LOT (n=115, Glofit-GemOx; n=57, R-GemOx) and 102 (37.2%) had ≥2 prior LOT (third-line+ 3L+; n=68, Glofit-GemOx; n=34, R-GemOx). Among 2L pts, early relapse (≤12 months mos after treatment) occurred in 120 pts (n=84, Glofit-GemOx; n=36, R-GemOx) and late relapse (12 mos after treatment) in 52 pts (n=31, Glofit-GemOx; n=21, R-GemOx). At the data cut-off, overall median OS follow-up was 35.1 mos (95% CI: 33.6–37.6). In pts aged 65y, median (95% CI) OS was 27.0 (13.7– not estimable NE) vs 9.0 (5.5–34.4) mos and PFS was 9.6 (5.8–NE) vs 5.2 (1.5–5.6) mos; CR rate (95% CI) was 58.2% (45.5–70.2) vs 26.5% (12.9–44.4) with Glofit-GemOx vs R-GemOx, respectively. In pts aged ≥65y, median (95% CI) OS was 25.0 (12.9–NE) vs 13.8 (7.6–18.5) mos and PFS was 15.8 (8.7–28.8) vs 3.0 (2.1–9.7) mos; CR rate (95% CI) was 58.6% (49.1–67.7) vs 24.6% (14.1–37.8) with Glofit-GemOx vs R-GemOx, respectively. In pts aged ≥75y, median (95% CI) OS was 33.0 (20.4–NE) vs 8.3 (3.8–15.7) mos and PFS was NE (17.0–NE) vs 2.6 (0.8–NE) mos; CR rate (95% CI) was 65.2% (49.8–78.7) vs 20.0% (5.7–43.7) with Glofit-GemOx vs R-GemOx, respectively. Median OS (95% CI) was NE (22.8–NE) vs 14.4 mos (10.3–26.8) in 2L pts and 17.0 (10.7–25.8) vs 6.7 mos (4.2–14.3) in 3L+ pts with Glofit-GemOx vs R-GemOx, respectively. Median PFS (95% CI) was 20.4 (9.2–NE) vs 5.5 (2.6–9.7) mos in 2L pts and 9.2 (5.4–18.3) vs 1.9 (1.4–3.6) mos in 3L+ pts with Glofit-GemOx vs R-GemOx, respectively. CR rate (95% CI) was 63.5% (54.0–72.3) vs 28.1% (17.0–41.5) in 2L pts and 50.0% (37.6–62.4) vs 20.6% (8.7–37.9) in 3L+ pts with Glofit-GemOx vs R-GemOx, respectively. In Glofit-GemOx-treated 2L pts with a CR at C4 (first tumor assessment), the 24-mo OS rate was 85.2% (95% CI: 75.7–94.7). In 2L pts with primary refractory DLBCL or early relapse, median (95% CI) OS was 19.2 (9.9–NE) vs 12.5 mos (6.9–16.5) and PFS was 9.2 (5.8–27.4) vs 2.6 (1.8–5.6) mos; CR rate (95% CI) was 56.0% (44.7–66.8) vs 16.7% (6.4–32.8); 36-mo OS (95% CI) rate was 46.1% (35.2–56.9) vs 16.5% (3.4–29.6) with Glofit-GemOx vs R-GemOx, respectively. In 2L pts with late relapse, median OS and PFS were NE in both arms; CR rate was 83.9% (66.3–94.6) vs 47.6% (25.7–70.2); 36-mo OS (95% CI) rate was 76.8% (59.5–94.1) vs 60.0% (36.9–83.1) with Glofit-GemOx vs R-GemOx, respectively. In the safety population (172 Glofit-GemOx-treated pts; 88 R-GemOx-treated pts), Glofit-GemOx had a well-characterized safety profile, supported by robust safety management guidance. Subgroup analysis findings, including by relapse status, age, and prior LOT, were generally consistent with those of the overall safety population and comparable between arms, after accounting for differences in exposure. The most frequently reported AEs were gastrointestinal disorders including nausea and diarrhea, cytopenias such as neutropenia and thrombocytopenia, and cytokine release syndrome (CRS). CRS occurred most frequently in pts aged ≥75y (52.4%) and was mainly low grade (Gr 1, 40.5%; Gr 2, 9.5%; Gr 3, 2.4%); no pts discontinued study therapy.Conclusions:Glofit-GemOx demonstrated superior survival and response outcomes vs R-GemOx, regardless of prior LOT and age, particularly in the 2L setting including in pts with primary refractory disease and early relapse. Safety was generally consistent in pt subgroups vs the overall population and in line with prior results.