Hypofractionation Radiotherapy in Combination With Glofitamab in Relapsed/Refractory Diffuse B-cell Lymphoma With Baseline High Tumor Burden

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.