Zanubrutinib in Combination With R-PolaCHP (ZaR-PolaCHP) for Newly Diagnosed Diffuse Large B-Cell Lymphoma

Inclusion Criteria: * Patients must have histologically confirmed DLBCL, irrespective of cell-of-origin. Patients with previously diagnosed indolent lymphoma (follicular lymphoma and marginal zone lymphoma but not small lymphocytic lymphoma) who have transformed to DLBCL are eligible only if they have not previously been treated for indolent lymphoma except for local radiation for early-stage disease * Patients may have received brief treatment with glucocorticoids (up to 250 mg/day prednisone or equivalent for a maximum of 10 days) and/or 1 cycle of chemotherapy such as R-CHOP (or some component\[s\] thereof) for the diagnosis of B-cell lymphoma provided they had staging computed tomography (CT) and/or positron emission tomography (PET)/CT scans prior to chemotherapy. Treatment must occur within 28 days prior to enrollment * Age \>= 18 years. Because no dosing or adverse event data are currently available on the use of zanubrutinib in combination with R-CHOP in patients \<18 years of age, children are excluded from this study * Eastern Cooperative Oncology Group (ECOG) performance status =\< 2. Performance status of 3 will be accepted if the impairment is caused by DLBCL complications and improvement is expected once therapy is initiated * Measurable disease (defined as \>= 1.5cm in diameter) or at least one PET fludeoxyglucose F-18 (FDG) avid area of disease * Patients must have adequate hematologic, hepatic, and renal function as defined below: * Hemoglobin \>= 7.0 g/dL *…