Inclusion Criteria: 

• Age > 18 years old.
• Previously untreated, newly diagnosed and histologically confirmed  DLBCL, not otherwise specified (NOS).
• Tumor tissue for retrospective central pathology review and correlative studies must be provided. 
• At least one bidimensionally measurable, PET positive disease site (greatest transverse diameter of ≥ 1.5 cm, greatest perpendicular diameter of ≥1.0 cm).
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
• International Prognostic Index (IPI) status of 2 to 5.
• Appropriate candidate for R-CHOP.
• Left ventricular ejection fraction (LVEF) of ≥ 50% assessed by echocardiography or cardiac multi-gated acquisition (MUGA) scan.
• Adequate hematologic, liver and renal function.
• 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.
• Males must:
  • use an effective barrier method of contraception if sexually active with FCBP;
  • refrain from donating sperm.
• In the opinion of investigator, the patient must be able and willing to receive adequate prophylaxis and/or therapy for thromboembolic events.

Exclusion Criteria:

• Any other histological type of lymphoma according to World Health Organization (WHO) 2016 classification of lymphoid neoplasms, known double- or triple-hit lymphoma.
• Transformed non-Hodgkin lymphoma (NHL) and/or evidence of composite lymphoma.
• History of radiation therapy to ≥ 5% of the bone marrow or history of anthracycline therapy.
• 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.
• History of myocardial infarction ≤ 6 months, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening arrhythmias.
• 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.