Glofitamab in Relapsed or Refractory Diffuse Large B-cell Lymphoma After CD19 Chimeric Antigen Receptor T-cell Therapy

A) Inclusion Criteria: 1. Signed informed consent form. 2. Age ≥ 18 years at the time of signing the informed consent form. 3. Histologically diagnosed diffuse large B-cell lymphoma, NOS initially, as defined by 2016 WHO guidelines and confirmed relapsed and refractory disease, defined as follows. * Relapsed: the disease that has recurred following a response that lasted over 6 months after completing the last line of therapy. * Refractory: the disease that did not respond to or that progressed less than 6 months after completion of the last line of therapy 4. RR-DLBCL patients who should undergo CD 19 CAR-T cell treatment prior to recruitment of this study have achieved partial response (PR) at one or three months after CAR-T cell infusion (If the patient achieves PR at one or three months, patients have to enroll within at least 3 months after CAR-T cell infusion.) 5. ECOG PS: 0-2 6. Adequate hematologic function, as defined by the following laboratory values (If cytopenia is associated with bone marrow involvement, the subject is excluded): * Absolute neutrophil \> 1,000/mm3 * Hemoglobin \> 9.0 g/dL (Transfusion free within 21 days prior to administration of glofitamab) * Platelet \> 75,000/mm3 (Transfusion free within 21 days prior to administration of glofitamab) * If the patient does not recover neutropenia at one month even though achieving PR, the investigator could wait until 3 months from first achieving PR at one month. However, the patient has to remain in PR status. 7. Negative SARS-CoV-2 antigen or PCR test within 7 days prior to enrollment 8. Adequate organ function, as defined by the following laboratory values * AST, ALT \< 3.0x upper limit of normal (ULN). * Total bilirubin \< 1.5 X ULN(Patients with a documented history of Gilbert's Syndrome and in whom total bilirubin elevations are accompanied by elevated indirect bilirubin are eligible if the total bilirubin is ≤ 3x ULN). * Serum creatinine ≤ 1.5 mg/dL, Creatinine clearance ≥ 50ml/min. 9. Female subjects are required to meet the following criteria: * Pregnancy test: For women of childbearing potential, a negative serum or urine pregnancy test at screening * Contraception: Patients must agree to either remain completely abstinent or to use two effective contraceptive methods that result in a failure rate of \< 1% per year from screening; until at least 3 months after pre-treatment with obinutuzumab, 2 months after the last dose of glofitamab, 2 months after the last dose of tocilizumab (if applicable), whichever is longer if the patient is a male. If the patient is female, effective contraception should be used until at least 18 months after pre-treatment with obinutuzumab, 2 months after the last dose of glofitamab, or 3 months after the last dose of tocilizumab (if applicable), whichever is longer.( Men must refrain from donating sperm during this same period) 10. Male subjects are required to meet the following criteria * With a female partner of childbearing potential or pregnant female partners, men must remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of \<1% per year for at least 6 months after the last dose of the study treatment. * Men must refrain from donating sperm during this study period. 11. Having tumor tissue samples in storage available for targeted sequencing 12. At least one bi-dimensionally measurable (≥ 1.5 cm) nodal lesion, or one bi-dimensionally measurable (≥1 cm) extranodal lesion, as measured on CT scan 13. Life expectancy ≥ 12 weeks B) Exclusion Criteria: 1. Patients have failed to respond to CD19 CAR-T cell therapy. 2. Patients who received previously treated bispecific antibodies. 3. Current or past history of primary or secondary central nervous system (CNS) lymphoma. 4. Peripheral neuropathy was assessed to be grade \>1 according to NCI CTCAE v5.0 at enrollment. 5. Current or past history of CNS disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease. \- Patients with a history of stroke who have not experienced a stroke of transient ischemic attack within the past 2 years and have no residual neurologic deficits, as judged by the investigator, are allowed. 6. Any of the following abnormal laboratory values, unless abnormal laboratory values are associated with the underlying lymphoma per the investigator. (Patients with a documented history of Gilbert's Syndrome and in whom total bilirubin elevations are accompanied by elevated indirect bilirubin are eligible if the total bilirubin is ≤ 3 × ULN) * AST/ ALT ≥ 3.0 X upper limit of normal (ULN). * Total bilirubin ≥ 1.5 X ULN. 7. Has a concomitant malignancy or had a malignancy (except for appropriately treated basal or squamous cell carcinoma or cervical carcinoma in situ) in the last 3 years prior to initiation of the study treatment 8. Underwent a major surgery within 21 days prior to initiating the study treatment or has not recovered from severe side effects of surgery 9. Concomitant use of immunosuppressants, except for the following: \- Intranasal, inhaled, or topical steroid, or local steroid injection (such as intra-articular injection) * Physiological dose ≤ 10 mg/day of prednisone or equivalent doses of systemic corticosteroid * Premedication with steroids to prevent hypersensitivity reaction (such as premedication prior to a CT scan). At the discretion of the investigator, the use of prednisolone at ≥10 mg for adrenal insufficiency may be acceptable. 10. Clinically significant or active cardiovascular disease * Myocardial infarction: within 6 months prior to study entry * Unstable angina, congestive heart failure (New York Heart Association class ≥III) or Objective Assessment Class C or D cardiac disease, or serious cardiac arrhythmias requiring medication, including any of the following: ➀ Left ventricular ejection fraction (LVEF) \< 50% as measured by echocardiography, ➁ QTc \> 480 msec (using the QTcF formula) on ECG at screening, ➂ unstable angina, ④ ventricular arrhythmias except for benign premature ventricular contractions, ⑤ medically uncontrolled supraventricular and nodal arrhythmias, ⑥ conduction abnormality requiring a pacemaker, ⑦ valve disease with documented cardiac dysfunction 11. Other concomitant severe and/or uncontrolled medical conditions (e.g., uncontrolled diabetes mellitus, chronic pancreatitis, active chronic hepatitis, etc.) that the investigator considers would preclude the subject's participation in the clinical trial. * Other severe acute or chronic medical conditions include colitis, inflammatory bowel disease, pneumonitis, pulmonary fibrosis, or psychiatric conditions, including recent (in the last 1 year) or active suicidal thoughts or behaviors; or laboratory abnormalities that, in the investigator's opinion, may increase the risk associated with participation in the clinical trial or study treatment, or that may interfere with the interpretation of clinical trial results. 12. Active infection or reactivation of a latent infection, whether bacterial, viral (including, but not limited to SARS-COV-2, EBV, cytomegalovirus (CMV), hepatitis B, hepatitis C, and HIV), fungal, mycobacterial, or other pathogens (excluding fungal infections of nail beds) or any major episode of infection requiring hospitalization or requiring systemic therapy within 4 weeks prior to the first study drug infusion. 13. Active autoimmune diseases may be exacerbated upon administration of immunostimulants. \- However, subjects with type I diabetes mellitus, vitiligo, psoriasis, or hypothyroidism, or hyperthyroidism not requiring immunosuppressive treatment are eligible. 14. Incapable of understanding or complying with clinical trial instructions and requirements or have a history of noncompliance with medical therapy 15. Pregnant or nursing (breastfeeding) women. \- Pregnancy is defined as the condition of a woman from pregnancy as confirmed by positive serum hCG laboratory test (\>5 mIU/mL) to termination of pregnancy. 16. Live vaccination is prohibited within 4 weeks prior to the first dose and during clinical trial participation. * However, inactivated vaccines such as, influenza and COVID vaccines are allowed. * Concomitant administration of an approved non-live COVID-19 vaccine is permitted. Examples of permitted vaccines include mRNA, inactivated virus, and replication-deficient viral vector vaccines. The decision on whether and when to administer a COVID-19 vaccine should be individualized by the investigator in consultation with the patient. * Factors to consider when making the individualized decision for patients receiving glofitamab include the following: * Risk of SARS-CoV-2 infection and potential benefit from the vaccine * The general condition of the patient and potential complications associated with SARS-CoV-2 infection * Severity and seriousness of the underlying disease * Epidemiology of COVID-19 in the Patient's Location * For patients who plan to receive a COVID-19 vaccine that requires two doses, it is recommended they complete the course of vaccination (i.e., they should receive the second dose) at least seven days before starting study treatment in order to maximize vaccine efficacy. For vaccines that require a single dose, patients are recommended to be vaccinated at least 28 days before starting study therapy in order to maximize vaccine efficacy unless a delay in treatment is clinically unacceptable. * If a COVID-19 vaccine is administered while the patient is already receiving treatment with glofitamab, the COVID-19 vaccine should be administered in the middle of a treatment cycle, for example, one week before or after a dose of glofitamab. The administration of the vaccine should be timed to take place after the completion of the glofitamab step-up dosing and at least one week after the administration of the target glofitamab dose. * Cytokine-release syndrome (CRS) is a risk for glofitamab that occurs most commonly during step-up dosing. Many COVID-19 vaccines are highly immunogenic, and their risk of potentiating CRS is unknown. 17. Hepatitis B virus (HBV) related liver disease, such as the following: * Chronic hepatitis with cirrhosis * HBV reactivation (Patients with occult or prior HBV infection (defined as negative HBsAg and positive hepatitis B core antibody \[HBcAb\]) may be included if HBV DNA is undetectable, provided that they are willing to undergo DNA testing on Day 1 of every cycle and every 3 months for at least 12 months after the last cycle of study treatment and appropriate antiviral therapy.) * Hepatitis B virus (HBV) infection at screening (HBV surface antigen-positive and HBV DNA-positive) 18. Hepatitis C virus (HCV) infection at screening (HCV RNA positive if positive for anti-HCV antibody at screening) \- Positive test results for hepatitis C virus (HCV) antibody - Patients who are positive for HCV antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA. 19. Known history of human immunodeficiency virus (HIV) seropositive status; for patients with unknown HIV status, HIV testing will be performed at screening. \- Individuals with a positive HIV test at screening are eligible, provided they are stable on antiretroviral therapy, have a CD4 count ≥ 200/μL, and have an undetectable viral load. HIV positive patients should be monitored per local/institutional standards while receiving study treatment. 20. Positive SARS-CoV-2 infection within 30 days prior to the first study treatment, including asymptomatic SARS-CoV-2 infection. \- Patients may be eligible if they have no persistent respiratory symptoms, no evidence of lung infiltrates on chest CT, and have a negative PCR during the 30 days prior to the first study treatment. 21. Known or suspected chronic active Epstein-Barr virus infection. 22. Prior solid organ transplantation. 23. Prior allogeneic stem cell transplantation. 24. History of Progressive multifocal leukoencephalopathy (PML). 25. Known or suspected history of HLH.