Real World Data of Glofitamab in Relapsed Refractory Large B-Cell Lymphoma in Non-Western Population from a Tertiary Center in Saudi Arabia
Authors: Albakr Rashed B. , Barradah Noha , Rasheed Walid , El Fakih Riad O. , Alshaibani Alfadel , Alhayli Saud , Alahmari Ali , Chaudhri Naeem A. , Alamer Abdullah , AlDalilah Yazeed M , AlRuwaili Ahmed A , AlSalloum Riyadh I , AlSugair Abdulaziz S , Samarkandi Hadeel H , Elhassan Tusneem Ahmed M , Aljurf Mahmoud , Albabtain Abdulwahab 
Published: December 2024

Abstract
Introduction:
DLBCL diffuse large B cell Lymphoma is the most common subtype of non-Hodgkin Lymphoma (NHL). Despite the recent advancement in the treatment of relapse refractory, which includes T-cell redirecting therapy, cellular therapies like chimeric antigen receptor T-cell (CAR-T) and Bispecific antibodies (bsAbs) there is significant unmet need and prognosis relatively poor,especially after failing CAR-T therapy. Glofitamabone of the first bsAbs to be FDA approved in June 2023 showed promising treatment options for patients who relapse after 2 lines of therapy. Glofitamab is a humanized monoclonal antibody targeting CD20 on B Cells and CD3 on T Cells of the Lymphoma tumor cells. We are reporting the outcomes and toxicity of Glofitamab in R/R DLBCL from King Faisal Specialist Hospital & Research Centre, a major academic center in Saudi Arabia.
Methods:
Glofitamab is available via compassionate use in Saudi Arabia for patients &gt;18 years and with relapsed/refractory Diffuse Large B Cell Lymphoma (DLBCL), transformed Follicular Lymphoma (tFL), High grade B-cell lymphoma NOS (HGBCL NOS), and Primary Mediastinal B Cell Lymphoma(PMBCL) who had received 3 prior lines of therapy. All patients received pretreatment with 1000 mg of obinutuzumab on day 1 of cycle(C) 1 Day (D) 1 to mitigate cytokine release syndrome, followed by a step-up dosing of 2.5 mg on C1D8 then 10 mg on C1D15 followed by 30 mg on C2D1 for a total of 12 cycles every 3 weeks. Patients were admitted only for C1D8 with the rest of the cycles given outpatient setting. We evaluated patient characteristics, Adverse events, Overall survival (OS), progression-free survival (PFS), Overall response rate (ORR), Complete Response (CR), Partial Response (PR) Progressive Disease (PD), and Stable Disease (SD) based on PET scan results.
Results:
30 patients were treated with Glofitamab from February 2022 until June 2024 and at least had one PET scan disease assessment after receiving at least 3 cycles of Glofitamab.
Median age 55 y.o. Males 56% (n=17), females44% (n=13). Median number of prior lines is 4 (3-7). Median number of cycles received 9.6 (3-12). 60% (n=18) were refractory to the previous line. 76.6% (n=23) had prior CAR-T. 16.6% (n=5) received Tisa-cel and 83.4% (n=25) received Axi-cel. DLBCL 76.6% (n=20), PMBCL 13.3% (n=4), HGBCL NOS 6% (n=2), Double Hit (DH) HGBCL6% (n=2), tFL 6% (n=2).
CR rates 26.6% (n= 8), PR rates 30% (n= 9), SD rate13.3% (n=4), PD rate 30% (n= 9). CR rates in patients who received prior CAR-T (n=23) was 17.3% (n=4). At a median follow-up of 12.3 months (4-26), 6- month PFS and OS were 39.6%and 42% respectively. The 12-month PFS and OS are 14 % and 17% respectively.
The most common adverse event was cytokine release syndrome (CRS), all occurred in C1D8 and C1D15. Grade 1 in 66% (n= 20), Grade 2, 21 % (N=6), and Grade 3+4, 6% (n= 2). Other adverse events: Neutropenia grade 1, 16% (n =5), grade 2, 36% (n=11), grade 3, 30% (n=9), grade 4, 10% of patients (n=3), and Thrombocytopenia grade 1, 50% (N=15), grade 2, 10% (N=3), grade 3, 6% (n=2) grade 4, 28% (n=8). 33.3% (n=10) required the use of GCSF for neutropenia.
Conclusion:
The presented data is reassuring that Glofitamab has an important role in the treatment of relapse refractory DLBCL, a real-world experience mainly of patients of Arab descent who are heavily pretreated, albeit response rates are less than what is reported in the registrational trial published by Dickenson et al. This data also suggests that Glofitamab can be an effective salvage therapy for relapsed B-Cell lymphoma post CAR-T with a reasonableresponse rate, especially in the absence of more effective therapies post CAR-T relapse. Glofitamab has a favorable toxicity profile and is administered safely in the outpatients for a fixed duration of time which is both convenient to the patient and healthcare provider.