Safety and efficacy of glofitamab for relapsed/refractory large B-cell lymphoma in a multinational real-world study

Abstract

Glofitamab, a bispecific antibody targeting CD20 and CD3, is approved for relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL) after at least 2 prior treatment lines, but real-world data are scarce. In this retrospective, multicenter, multinational study, we evaluated the outcomes of 70 patients with r/r DLBCL treated with glofitamab as part of the compassionate use patient program in Germany, Austria, and Switzerland. The median number of prior treatment lines was 4, with 71% of patients refractory to their last treatment. Cytokine release syndrome was observed in 40% of patients (grade 3-4 in 2%), immune effector cell-associated neurotoxicity syndrome in 10% (grade 3 in 1%), and infections in 31% (grade 5 in 3%). The overall response rate was 46%, with 27% achieving complete responses (CR) and 19% partial responses. The median progression-free survival (PFS) was 3.6 months, whereas the median overall survival was 5.7 months. Notably, 13 patients (19%) were in CR 6 months after initiating glofitamab and exhibited durable responses. Elevated lactate dehydrogenase is the most robust predictor of inferior outcome. Patients pretreated with bendamustine within 6 months prior to glofitamab initiation exhibited significantly reduced PFS, suggesting that bendamustine may impair T-cell fitness and hence glofitamab efficacy. In summary, glofitamab demonstrates promising efficacy and a manageable safety profile in heavily pretreated patients with r/r DLBCL in a real-world scenario and the optimal sequence of treatments should use T-cell-depleting agents before glofitamab with caution.

Graphical abstract

Figure 1.

Patient trajectories. Swimmer plot visualizes timing of response and DOR and highlights treatment in all patients of this cohort.

Figure 2.

CRS and ICANS after glofitamab. Incidence of CRS (A) and ICANS (B) in all patients by grades.

Figure 3.

Survival proportions after treatment initiation with glofitamab and outcomes for clinically relevant patient (pt) subsets. (A) PFS for all pts; (B) OS for all pts; (C) PFS in CAR-T–naive (blue) and CAR-T–exposed (red) pts; and (D) OS in CAR-T–naive (blue) and CAR-T–exposed (red) pts. (E-F) Landmark analysis for PFS (E) and OS (F) in pts depending on response 180 days after start of glofitamab (CR, red; non-CR, blue). (G-H) PFS (G) and OS (H) for pts treated before glofitamab with Benda-containing regimes (red, >6 months; blue, ≤6 months). The P values are obtained using a log-rank test and pts at risk are highlighted below the Kaplan-Meier plot. Benda, bendamustine; exp., exposed; nai., naive.

Figure 4.

Survival proportions stratified by pathological subtypes. PFS (A) and OS (B) for patients stratified by DLBCL NOS (red), transformed DLBCL (blue), and HGBL (green). The P values are obtained using a log-rank test and patients at risk are highlighted below the Kaplan-Meier plot.