Glofitamab has shown efficacy and safety in the treatment of patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) and has been approved for marketing in China. However, in patients with baseline high tumor burden, the complete response (CR) rate is relatively lower compared with patients without. There is still a need to improve the efficacy of glofitamab in patients with high tumor burden. Previous studies have shown that hypofractionation radiotherapy (HRT) may induce T cell immune responses and improve the tumor microenvironment . Evidence shows that radiotherapy (RT) improves chimeric antigen receptor T-cell (CAR-T) efficacy as a bridging therapy . Based on the experience of RT combined with CAR-T, bispecific antibodies, as another T-cell therapy, may also demonstrate synergistic effects when combined with HRT, especially in those patients with bulky disease. This study will enroll R/R DLBCL patients with high tumor burden to assess the efficacy and safety of glofitamab in combination with HRT and to explore a new treatment model for R/R DLBCL patients with high tumor burden at baseline.

Inclusion Criteria:

• Signed informed consent.
• Aged 18-75 years at the time of signing the informed consent, willing to follow and able to complete all study procedures.
• Expected survival ≥ 12 weeks.
• ECOG performance status score of 0-2 points ;
• Patients with CD20-positive DLBCL confirmed by pathological histology; (unspecified DLBCL, HGBCL, PMBCL, FL-transformed DLBCL).
• R/R DLBCL who have received at least one line of systemic treatment (including at least 2 cycles of rituximab-containing immunochemotherapy).
• Baseline high tumor burden, defined as tumor diameter > 6 cm and/or TMTV > 128.7 mL .
• HIV test results were negative at screening, except for the following: HIV-positive patients who have been receiving stable antiretroviral therapy and CD4 count ≥ 200/µL before enrollment Patients with undetectable viral load can be enrolled.
• Women of childbearing age with negative urine or blood pregnancy test within 7 days before enrollment need to agree to take effective contraceptive measures during treatment and follow-up.

Exclusion Criteria:

• Individuals who have drug allergies or metabolic disorders to the drugs in this protocol.
• Previous recipients of allogeneic organ transplants.
• Individuals who received systemic immunotherapy within 4 weeks or 5 half-lives (whichever is shorter) of the drug.
• Anti-cancer drug treatment within 28 days before the start of treatment
• Prior radiotherapy in the mediastinum/pericardium area; radiation therapy for non-target lesion sites is allowed.
• History of severe or extensive cardiovascular disease.
• Recent major surgery (within 4 weeks before the start of Cycle 1), excluding diagnostic surgeries.
• Currently suffering from active CNS lymphoma.
• Known or suspected history of hemophagocytic lymphohistiocytosis (HLH)
• Current or previous history of concurrent Waldenström's macroglobulinemia.
• Known active infection at the time of enrollment in the study.
• Immune-related adverse events that appeared during prior immunotherapy: ≥Grade 3 adverse events, except for Grade 3 endocrine diseases controlled by alternative therapies. Grade 1 or 2 adverse events that did not return to baseline levels after stopping treatment.
• History of autoimmune diseases (long-standing or well-controlled autoimmune diseases, hypothyroidism, immune thrombocytopenic purpura, and well-controlled Type I diabetes are excluded).
• Abnormal coagulation function: INR or PT >1.5× upper limit of normal (ULN), PTT or aPTT >1.5× ULN.
• Suspected or latent tuberculosis (confirmed by positive IFNγ release test)
• Active hepatitis B virus (HBV) infection/positive HCV RNA test for hepatitis C virus (HCV)/HIV seropositive.
• Previously suffered from other invasive malignancies, excluding early-stage cervical cancer, basal cell carcinoma of the skin, and thyroid cancer .
• Pregnant or breastfeeding, or planning to become pregnant during the study period or within 18 months after pre-treatment with obinutuzumab or within 2 months after the last dose of glofitamab (whichever is longer).
• Other concurrent uncontrolled medical conditions that, in the investigator's opinion, would affect the patient's participation in the study.