Major Inclusion Criteria:

1. Age >18 years
2. Histologically confirmed diagnosis of DLBCL, not otherwise specified (NOS)
3. Tumor tissue for retrospective central pathology review and correlative studies must be provided.
4. At least one bidimensionally measurable, PET positive disease site (greatest transverse diameter of ≥1.5 cm, greatest perpendicular diameter of ≥1.0 cm)
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
6. International Prognostic Index (IPI) status of 2 to 5
7. Appropriate candidate for R-CHOP
8. Left ventricular ejection fraction (LVEF) of ≥50% assessed by echocardiography or cardiac multi-gated acquisition (MUGA) scan
9. Adequate hematologic, liver and renal function
10. Females of childbearing potential (FCBP) must:
    • not be pregnant
    • refrain from breast feeding and donating oocyte
    • agree to ongoing pregnancy testing
    • commit to continued abstinence from heterosexual intercourse, or agree to use and be able to comply with the use of double-barrier contraception
11. Males must:
    • use an effective barrier method of contraception if sexually active with FCBP
    • refrain from donating sperm
12. In the opinion of investigator, the patient must be able and willing to receive adequate prophylaxis and/or therapy for thromboembolic events

Major Exclusion Criteria:

1. Any other histological type of lymphoma according to World Health Organization (WHO) 2016 classification of lymphoid neoplasms, known double- or triple-hit lymphoma
2. Transformed non-Hodgkin lymphoma (NHL) and/or evidence of composite lymphoma
3. History of radiation therapy to ≥25% of the bone marrow or history of anthracycline therapy
4. History of prior non-hematologic malignancy except for the following:
   • Malignancy treated with curative intent and with no evidence of active disease present for more than 2 years before screening
   • Adequately treated lentigo maligna melanoma without current evidence of disease or adequately controlled non-melanomatous skin cancer
   • Adequately treated carcinoma in situ without current evidence of disease
5. History of myocardial infarction ≤6 months, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening arrhythmias
6. Patients with:
   • positive test results for active hepatitis B and C
   • known seropositive for or history of active viral infection with human immunodeficiency virus (HIV)
   • known active bacterial, viral, fungal, mycobacterial, or other infection at screening
   • known central nervous system (CNS) lymphoma involvement
   • history or evidence of clinically significant cardiovascular, CNS and/or other systemic disease that would in the investigator opinion preclude participation in the study