The Efficacy and Safety of Pola-ZR-Glo in Older Treatment-naive Patients With LBCL

• Pola-ZR-Glo (Polatuzumab Vedotin, Zanubrutinib, Lenalidomide and Glofitamab) regimen (Drug): Pola-ZR-Glo (Polatuzumab Vedotin, Zanubrutinib, Lenalidomide and Glofitamab) regimen will be given from day 1 of each cycle of treatment. Each cycle will last for 21 days. Participants will receive a total of 12 cycles. Dosage: Polatuzumab vedotin (1.8 mg/kg) will be administered intravenously on Day 2 of Cycle 1 and on Day 1 of Cycles 2-6 (each Q3W). Zanubrutinib (160mg bid p.o.) will be administered from D1 to D21 through Cycles 1-6 Q3W. Lenalidomide (25mg qd p.o.) will be administered from D2 to D11 through Cycles 1-6 Q3W. Glofitamab will be administered i.v. on a step-up dosing schedule starting on Day 8 of Cycle 1 (2.5 mg), Day 15 of Cycle 1 (10 mg), followed by 30 mg on Day 1 of Cycles 2-12, with each cycle being 21 days. A single dose of obinutuzumab 1000 mg will be administered intravenously on Day 1 of Cycle 1.

Primary outcomes

• Progression free survival [Baseline up to data cut-off (up to approximately 2 years)]

Secondary outcomes

• Event-free survival [Baseline up to data cut-off (up to approximately 2 years)]
• Complete response rate [At the end of Cycle 3, 6 and at the end of treatment (each cycle is 21 days)]
• Objective response rate [At the end of Cycle 3, 6 and at the end of treatment (each cycle is 21 days)]
• Overall Survival [Baseline up to data cut-off (up to approximately 2 years)]
• DoR [From documentation of CR/PR until relapse/progression or death due to any reason without documented relapse, whichever came first, assessed up to 32 months.]
• Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v6.0 [From enrollment to study completion, a maximum of 4 years]
• Patient reported outcome [Day 1 of Cycles 1, 4 and 7 (Cycle length=21 days); 30 days after treatment completion]: Quality of Life will be assessed by EORTC QLQ-C30 (Verison 3.0), EORTC QLQ-ELD14 and FACT-Lym LymS.

Sex: All, ages: 70 Years to any

Inclusion Criteria:

Patients must satisfy all of the following criteria to be enrolled in the study:

* Histologically-confirmed large B-cell lymphoma (without central nervous system involvement)
* Aged ≥ 70 years old with comprehensive geriatric assessment stratified as unfit or frail, or those who decline immunochemotherapy.
* Eastern Cooperative Oncology Group Performance Status 0-2
* At least 1 measurable site of disease (defined as lymph nodes with the long diameters longer than 1.5cm, or extra-nodal sites with the long diameters longer than 1.0cm; meanwhile, any lesion site with at least 2 measurable vertical diameters)
* Life expectancy of at least 3 months determined by researchers
* The patient or his or her legal representative must provide written informed consent prior to any special examination or procedure for the research.
* Anti-lymphoma drugs have not been used before (except glucocorticoids)

Exclusion Criteria:

Presence of any of the following criteria will exclude a patient from enrollment:

* Uncontrolled blood clotting disorders, connective tissue diseases, serious infectious diseases and other diseases
* Laboratory measures meet the following criteria at screening (unless caused by lymphoma):

Neutrophils<1.0×10\^9/L Platelets<75×10\^9/L ALT or AST is 2.5 times higher than the upper limits of normal (ULN), serum bilirubin are 1.5 times higher than the ULN.

eGFR is lower than 30ml/min/1.73m\^2 (according to Cockcroft-Gault Equation or MDRD Equation).

* uncontrollable or significant cardiovascular diseases, including but not limited to: Left ventricular ejection fraction<50% Cardiomyopathy, such as dilated cardiomyopathy, hypertrophic cardiomyopathy, restrictive cardiomyopathy QTc prolongation with clinical significance, QTc interval>470ms (females) or 480ms (males), type 2 second-degree atrioventricular block or third-degree atrioventricular block
* Patients with HbsAg positive are required to have HBV DNA<1.0×10\^3 IU/ml before entering the group. In addition, if the patient is HBsAg negative but HBcAb positive (regardless of HBsAb status), HBV DNA test is also required, and HBV DNA<1.0×10\^3 IU/ml is required before entering the group
* Patients with psychiatric disorders or patients who are known or suspected to be unable to fully comply with the study protocol
* HIV-infected patients
* History of stroke or intracranial hemorrhage within 6 months prior to start of therapy
* Other medical conditions determined by the researchers that may affect the study