• Previously untreated patients with local biopsy-proven, CD20-positive DLBCL, including one of the following diagnoses by 2016 World Health Organization (WHO) classification of lymphoid neoplasms are eligible:

‣ DLBCL, NOS including GCB type, ABC type

⁃ T-cell rich large BCL

⁃ Epstein-Barr virus-positive DLBCL, NOS

⁃ Anaplastic lymphoma kinase (ALK)-positive large BCL

⁃ Human herpes virus-8 (HHV8)-positive DLBCL, NOS

⁃ High-grade BCL with MYC and B-cell lymphoma 2 (BCL2) and/or B-cell lymphoma 6 (BCL6) rearrangements (double-hit or triple-hit lymphoma). Please note: Patients must be appropriate candidates for R-CHOP. If an investigator deems a patient with a known double- or triple-hit lymphoma (HGBL) should be treated more aggressively (e.g. dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin and rituximab \[DA-EPOCH-R\] or cyclophosphamide, vincristine, doxorubicin and dexamethasone (CVAD) followed by methotrexate and cytarabine \[Hyper CVAD\]), this patient would not be considered eligible for this study

⁃ HGBL-NOS

⁃ DLBCL coexistent with either follicular lymphoma (FL) of any grade, gastric MALT lymphoma or non-gastric MALT lymphoma

⁃ FL grade 3b

• Availability of archival or freshly collected tumor tissue sent for retrospective central pathology review

• IPI status of 3 to 5 (for patients \> 60 years of age) or aaIPI 2 to 3 (for patients ≤ 60 years of age)

• Diagnosis to treatment interval, defined as the time between the date of DLBCL diagnosis (date of the first biopsy specimen containing B Cell lymphoma according to the local pathology report) and the start of treatment (C1D1) ≤ 28 days

• ECOG performance status of 0, 1, or 2

• Left ventricular ejection fraction equal to or greater 50% as assessed by local echocardiography or cardiac multi-gated acquisition (MUGA) scan

• Adequate hematologic function

• Female participants: Agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods and refrain from breast feeding and donating eggs; agreement to ongoing pregnancy testing during the course of the study, and after study therapy has ended

• Male participants: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom and agreement to refrain from donating sperm