Glofitamab Combined with Salvage Therapy for Relapsed or Refractory Diffuse Large B-Cell Lymphoma: A Real-World Prospective Observational Study in Chinese Patients
Authors: Gu Jingxian , You Tao , Xu Peng , Xiao Jiebing , Dai Wei , Jin Zhengming , Ma Xiao , Wu Depei , Huang Haiwen 
Published: December 2024

Background: Several clinical trials have demonstrated the remarkable effectiveness of glofitamab, a CD20xCD3 bispecific antibody, in patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL). However, real-world data on this drug remains limited. Here, we present the clinical outcomes of R/R DLBCL patients with high-risk prognostic factors in a real-world setting who have received glofitamab in combination with salvage therapy as at least 2nd line of therapy. This prospective observational study was approved by the institutional review board (20240430041615581), and registered on ClinicalTrials.gov (NCT06497452).

Methods:R/R DLBCL patients aged ≥18 years received glofitamab plus salvage therapy including lenalidomide, Bruton Tyrosine Kinase inhibitor, polatuzumab vedotin, venetoclax, etoposide, rituximab, cytarabine, GemOx (gemcitabine and oxaliplatin) regimen and EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) regimen. Obinutuzumab 1000mg was administered on Cycle (C) 1 Day (D) 1 as pretreatment, followed by a step-up dosing of glofitamab on C1D8 (2.5mg), C1D15 (10mg) and D1 from C2 (30mg). Salvage therapy was given at the standard dose per the study protocol. Safety was evaluated during each cycle. Efficacy was assessed using positron-emission tomography-computed tomography at screening and every two cycles.

Results:As of July 21, 2024, a total of 18 patients were enrolled in this study. 16 patients (5 female and 11 male) were included in the analysis. 2 patients dropped out during the first cycle. All 16 patients who completed at least one cycle were subjected to safety evaluation. 15 patients were assessed for efficacy, as 1 patient failed to receive evaluation after the first cycle. The median age was 56.5 years (range: 28-80). Of the 16 DLBCL patients, 2 were transformed from chronic lymphocytic leukemia (Richter syndrome), and 1 had transformed follicular lymphoma. All the patients had advanced disease (Ann Arbor stage III/IV: 3/13) with a median International Prognostic Index of 3.0 and a median Eastern Cooperative Oncology Group performance status of 2.0. High-risk abnormal genetic factors mainly include BCL6 and MYC rearrangement (double-hit lymphoma; 2/16) and TP53 mutation (5/16). 3 had bone marrow involvement at diagnosis. 3 had bulky disease (≥7cm) and 1 had secondary central nervous system involvement at study entry. Patients had received a median of 2 (range: 1-7) lines of prior therapies. 2 patients underwent autologous stem-cell transplantation (ASCT), and another 2 had received chimeric antigen receptor (CAR) T-cell therapies previously. 37.5% (6/16) were refractory to the last previous therapy, and 62.5% (10/16) relapsed after the last previous therapy. The median number of cycles patients underwent was 2.0 (range: 1-5).

The overall response rate (ORR) and complete response (CR) (as best response) rate in 15 efficacy-evaluable patients were 80.0% (12/15) and 46.7% (7/15), respectively. All the CRs were ongoing at the data cut off. Median overall survival and median progression-free survival were not reached. 1 patient discontinued after two cycles and then received ASCT combined with CART therapy with the 2-cycle assessment of partial response. Among the 16 safety-evaluable patients, 11 patients (68.7%) experienced cytokine release syndrome (CRS). Most of the CRS events were low grade (Grade 1: 37.5%; Grade 2: 25.0% ). Only 1 patient (6.2%) experienced Grade 3 CRS event. No cases of immune effector cell-associated neurotoxicity syndrome were reported. The most common Grade 3/4 adverse event (AE) was neutropenia (9/16; 56.2%), which was mainly due to the combined chemotherapeutic drugs. No Grade 5 AEs were reported. None of the AEs led to the discontinuation of glofitamab-based combination therapy.

Conclusions: The preliminary results of this prospective study demonstrate the effectiveness and safety of the glofitamab-based salvage therapy for heavily pre-treated patients with high-risk prognostic factors in the real-world setting. Updated analyses, including further follow-up data and exploratory applications of glofitamab, will be presented.