The Clinical Efficacy and Safety of Glofitamab in Chinese Relapsed or Refractory Large B-Cell Lymphoma

Background: Large B-cell lymphoma (LBCL) is a common and aggressive disease and the prognosis of relapsed/refractory(R/R) LBCL is poor. Glofitamab is reported to have 35% complete responses (CR) in these heavily treated patients. To better understand the efficacy and safety of Glofitamab in Chinese R/R LBCL patients in a real-world setting, we conducted a multi-center, non-interventional study of Glofitamab in R/R LBCL. Here we analyzed and reported the clinical outcomes of 21 R/R DLBCL treated with Glofitamab in our center.

Methods: We included patients who had histologically confirmed R/R DLBCL, transformed follicular lymphoma, high-grade B-cell lymphoma, or Burkitt's lymphoma. All the patients had disease that had relapsed after, or was refractory to, at least two previous lines of therapy including at least one anti-CD20 antibody-containing regimen and at least one anthracycline-containing regimen. We reported the best objective response rate (bORR), best complete response (bCR) rate, and adverse events of special interest (AESI), including cytokine release syndrome (CRS), infection, neurological events (NE), and immune effector cell-associated neurotoxicity syndrome (ICANS).

Results: To the cut-off date of Jul 25, 2024, a total of 21 R/R LBCL patients had undergone efficacy evaluation at Cycle 2 (C2). The median age of patients was 61 (range 23,76) years, with 11 patients (52.4%) aged 60 years or older, and 11 (52.4%) patients were male. The baseline characteristics of these patients included 16 (76.1%) with diffuse large B-cell lymphoma, 1 (4.8%) with high-grade B-cell lymphoma, 3 (14.3%) with transformed follicular lymphoma, and 1 (4.8%) with Burkitt's lymphoma. 52.4% of patients had an International Prognostic Index (IPI) score ≥3. The median number of prior treatments was 2, while 9 patients (42.8%) had received 3 or more previous therapies and 9 patients (42.8%) had undergone Chimeric Antigen Receptor T-Cell Therapy (CAR-T). Glofitamab is used as bridging therapy of CAR-T in 6 patients (28.6%) and 5 had CR/PR, but 1 with PD before CAR-T infusion. In addition, 3 (14.3%) patients with PD after CAR T infusion were evaluated for CR/PR after Glofitamab treatment. Notably, compared to the baseline characteristics of Glofitamab real-world studies for R/R LBCL in other countries, a greater proportion of Chinese patients had an Eastern Cooperative Oncology Group performance status (ECOG PS) score ≥2 (52.4%). Most patients had advanced disease (Ann Arbor stage III or IV disease in 71.4%), LDH was elevated in 15 patients (71.4%), and MYC, BCL-2 double expression was found in 10 patients. The median follow-up was 10.1 months. The C2 bORR and bCR rate was 76.1% and 42.8% respectively. The median progression-free survival (PFS) reached 10.8 months, with PFS rates of 83.1% at 12 months, an estimated 62.3% at 24 months. No new safety signals were observed in the treated population. CRS of any grade occurred in 13 patients (61.9%), with 12 patients (57.1%) experiencing grade 1 and 1 patient (4.8%) experiencing grade 2. NE of any grade occurred in 2 patients (9.5%), No grade 5 CRS or NE appeared.

Conclusions: This study demonstrated the consistent efficacy of Glofitamab in Chinese R/R DLBCL patients, while the incidence of adverse events such as CRS and NE was lower. Glofitamab is not only effective in patients with CAR-T failure, but also could boost CAR-T efficacy as a bridging therapy to decrease the tumor mass and yield even greater benefits.

No relevant conflicts of interest to declare.