Résumé
Fixed-duration glofitamab monotherapy induced high complete response (CR) rates with manageable safety in relapsed/refractory (R/R) large B-cell lymphoma (LBCL; NCT03075696). We present extended follow-up and subgroup analyses in patients with prior chimeric antigen receptor T-cell therapy (CAR-T) and by baseline total metabolic tumor volume (TMTV).
Patients with LBCL and ≥2 prior therapies received obinutuzumab pretreatment (1000mg) on Day (D)1 of Cycle (C)1, then intravenous glofitamab step-up doses during C1 (D8: 2.5mg; D15: 10mg) and target dose (30mg) on D1 of C2–12. Primary endpoint: independent review committee (IRC)-assessed CR rate. Exploratory analyses of baseline TMTV association with progression-free survival (PFS) and cytokine release syndrome (CRS) events (ASTCT criteria) were investigated. All patients provided informed consent.
As of September 4, 2023, 154/155 patients received ≥1 dose of study treatment. Baseline characteristics were previously presented (Dickinson et al. NEJM 2022). IRC-assessed overall response and CR rates were 52% and 40%, respectively; most CRs (34/62; 55%) were ongoing at data cut-off. Median duration of CR (DoCR) was 26.9 months (95% confidence interval [CI]: 19.8–not evaluable [NE]). In patients with CR at end of treatment, 18-month PFS and overall survival rates were 67% and 81%, respectively. In patients with prior CAR-T (n=52), CR rate (37%) was consistent with the overall population (40%); median DoCR was 22.0 months (95% CI: 6.7–NE). No new safety signals were observed. Median baseline TMTV (n=144) was 128.7mL (range: 0–3820). Grade ≥2 CRS occurred in 2.8%, 11.1%, 16.7%, and 38.9% of patients in the first– fourth TMTV quartiles, respectively (Chi-square=16.273; degrees of freedom=1; P<.0001). In patients with baseline TMTV above/equal to (n=72) versus below (n=72) the median, 24-month PFS rates (95% CI) were 11.8% (6.0–23.5) and 41.6% (31.1– 55.6), respectively (hazard ratio: 2.4; 95% CI: 1.6–3.6).
Glofitamab showed durable responses in patients with R/R LBCL, with no new safety signals; this was consistent in patients with prior CAR-T, demonstrating long-term outcomes and suggesting a curative potential with fixed-duration glofitamab in R/R LBCL. Higher baseline TMTV was associated with increased risk of Grade ≥2 CRS and may be prognostic for PFS.