Background The bispecific antibody (BsAb) glofitamab (G) has demonstrated high efficacy and acceptable feasibility in patients with aggressive relapsed/refractory (r/r) B-cell lymphoma in clinical trials. However, real-world evidence on its use remains limited, particularly in the context of evolving immunotherapy options and their sequencing. Here we report outcomes of glofitamab in CAR-T naive patients from a compassionate use program (CUP) and routine clinical practice.

Materials and methods This multicenter retrospective study included CAR-T naive patients with r/r B-cell lymphoma who were treated with G within CUP or routine clinical practice in 22 Russian centers. Glofitamab was administered according to the approval study.

The analysis included evaluation of overall response (ORR) and complete response (CR) rate, overall survival (OS), progression-free survival (PFS). We assessed the impact of clinical factors on CR achievement and PFS, along with characterization of adverse events (AEs).

Results As of July 2025, 152 patients were enrolled. Median age at G initiation was 51 (19-83), male/female ratio - 72/80 (47/53%). The study population included patients with diffuse large B-cell lymphoma, both de novo and transformed (n=88, 58%), high-grade B-cell lymphoma (n=17, 11%), primary mediastinal large B-cell lymphoma (n=20, 13%), follicular large B-cell lymphoma (n=9, 6%) and other lymphomas (n=18, 12%). Median number of therapy lines before G was 3 (3-9). Overall, 122 patients (80%) had primary refractory/early relapsed disease, and 56 (37%) presented with Bulky disease (>7.5 cm) at G initiation. Twenty-four patients (16%) underwent auto-HCT, and 2 (1%) allo-HCT previously.

The ORR, available for 150 of 152 patients, was 58% (n=87), comprising 45% CR and 13% partial remission (PR). Median follow up was 9.3 months (0.6-51.9). At the last follow-up, 143 (94%) pts discontinued therapy due to: end of treatment after 12 cycles (n=46, 32%), disease progression (n=69, 48%), infections (n=18, 12%, including COVID19 in 15 pts, 10%) or other reason (n=10, 7%). Median PFS was 5.8 months (CI 95%: 3.8-10.7), 1-year PFS 39.4% (CI 95%: 32.1-48.4); median OS was 17.9 months (CI 95%: 12.4-NA), 1-year OS was 59% (CI 95%: 51.2-67.9). Median OS and PFS in patients with CR were not reached; with median follow up 15.6 months (3.2-52), estimated 2-year PFS and OS were 72.8% (CI 95%: 61.3-86.5) and 81.3% (CI 95%: 70.9-93.1) respectively. In contrast, patients with PR demonstrated significantly worse outcomes, with median PFS of 5.5 months (CI 95%: 3.7-NA) and OS of 14.2 months (CI 95%: 8.4-NA).

Recent bendamustine administration (≤3 months) prior to G initiation was associated with lower rate of CR (OR 0.31, 95% CI 0.14-0.66, p=0.003) and shorter PFS (3.6 vs 8.8 months, 95% CI 1.13-2.63, HR=1.72, p=0.01). Other risk factors for CR achievement and PFS duration included: ECOG PS >1 (CR: OR 0.41, 95% CI 0.20-0.83, p=0.016; PFS: HR 2.13, 95% CI 1.41–3.22, p=0.004), B symptoms (CR: OR 0.38, 95% CI 0.16-0.84, p=0.021; PFS: HR 2.06, 95% CI 1.32–3.21, p=0.001), and Bulky disease >7.5 cm (CR: OR 0.40, 95% CI 0.20-0.80, p=0.010; PFS: HR 1.91, 95% CI 1.26–2.90, p=0.002).

Any grade AEs were observed in 132 patients (87%) including grade ≥3 AEs in 57 patients (38%). Grade 5 AEs were reported in 10 patients (7%). Any grade cytokine release syndrome (CRS) was observed in 63 (41%) pts with only 3 patients (2%) experiencing grade 3 CRS. No cases of immune effector cell-associated neurotoxicity syndrome (ICANS) were documented. Infectious AEs occurred in 68 patients (45%), including grade ≥3 AEs in 20 patients (13%; with COVID-19 grade 5 AEs in 10 pts, 7%).

Conclusion Glofitamab demonstrates high efficacy in CAR-T naive r/r B-cell lymphoma patients with CR rates comparable to the approval study in a real-world scenario. Notably, ECOG PS, B symptoms, Bulky disease and bendamustine exposure within 3 months prior to G initiation were associated with reduced incidence of CR and worse PFS.

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2025
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