Inclusion Criteria:

• Histologically proven large B-cell lymphoma including the following types defined by WHO 2016 (Swerdlow et al., 2016):
  • DLBCL not otherwise specified (including ABC/GCB);
  • HGBL with or without MYC and BCL2 and/or BCL6 rearrangement;
  • DLBCL arising from FL o T-cell/histiocyte rich large B-cell lymphoma;
  • DLBCL associated with chronic inflammation;
  • Primary cutaneous DLBCL, leg type;
  • Epstein-Barr virus (EBV) + DLBCL.
• Relapsed or refractory disease after first-line chemoimmunotherapy:
  • Refractory disease defined as no complete remission to first-line therapy; subjects who are intolerant to first-line therapy are excluded.  Progressive disease (PD) as best response to first-line therapy;
  • Stable disease (SD) as best response after at least 4 cycles of first-line therapy (e.g., 4 cycles of R-CHOP);
  • PR as best response after at least 6 cycles and biopsy-proven residual disease or disease progression ≤ 12 months of therapy.
• Relapsed disease defined as complete remission to first-line therapy followed by biopsy-proven disease relapse ≤ 12 months of first-line therapy.
• Subjects must have received adequate first-line therapy including at a minimum:
  • Anti-CD20 monoclonal antibody unless investigator determines that tumor is CD20 negative; and
  • An anthracycline containing chemotherapy regimen.
• Intent to proceed to HDT and ASCT if response to second-line therapy.
• Subjects must have radiographically documented disease.
• No known history or suspicion of central nervous system (CNS) involvement by lymphoma.
• At least 2 weeks or 5 half-lives, whichever is shorter, must have elapsed since any prior systemic cancer therapy at the time the subject provides consent.
• Age 18 years or older at the time of informed consent.
• ECOG performance status of 0 or 1.
• Adequate bone marrow, renal, hepatic, pulmonary and cardiac function defined as:
  • Absolute neutrophil count (ANC) ≥1000/μL;
  • Platelet count ≥ 75,000/μL;
  • Absolute lymphocyte count ≥ 100/μL;
  • Creatinine clearance (as estimated by Cockcroft Gault) ≥ 60 mL/min;
  • Serum alanine aminotransferase/aspartate aminotransferase (ALT/AST) ≤ 2.5 upper limit of normal (ULN);
  • Total bilirubin ≤ 1.5 mg/dl, except in subjects with Gilbert’s syndrome;
  • Cardiac ejection fraction ≥ 50%, no evidence of pericardial effusion as determined by an echocardiogram (ECHO), and no clinically significant electrocardiogram (ECG) findings;
  • No clinically significant pleural effusion;
  • Baseline oxygen saturation > 92% on room air.
• Females of childbearing potential must have a negative serum or urine pregnancy test (females who have undergone surgical sterilization or who have been postmenopausal for at least 2 years are not considered to be of childbearing potential).

Exclusion Criteria:

• History of malignancy other than nonmelanoma skin cancer or carcinoma in situ (e.g., cervix, bladder, breast) unless disease free for at least 3 years.
• History of Richter’s transformation of CLL or PMBCL.
• History of autologous or allogeneic stem cell transplant.
• Received more than one line of therapy for DLBCL.
• Prior CD19 targeted therapy.
• Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and IL-2) within 6 weeks or 5 half-lives of the drug, whichever is shorter, prior to the first dose of axicabtagene ciloleucel or SOC.
• Prior chimeric antigen receptor therapy or other genetically modified T-cell therapy or prior randomization into ZUMA-7.
• History of severe, immediate hypersensitivity reaction attributed to aminoglycosides.
• Presence of fungal, bacterial, viral, or other infection that is uncontrolled or requiring intravenous (IV) antimicrobials for management. Simple urinary tract infection (UTI) and uncomplicated bacterial pharyngitis are permitted if responding to active treatment.
• Known history of infection with human immunodeficiency virus (HIV) or hepatitis B (HBsAg positive) or hepatitis C virus (anti-HCV positive). If there is a positive history of treated hepatitis B or hepatitis C, the viral load must be undetectable per quantitative polymerase chain reaction (PCR) and/or nucleic acid testing.
• Active tuberculosis.
• Presence of any indwelling line or drain (eg, percutaneous nephrostomy tube, indwelling Foley catheter, biliary drain, or pleural/peritoneal/pericardial catheter). Dedicated central venous access catheters, such as a Port-a-Cath or Hickman catheter, are permitted.
• Subjects with detectable cerebrospinal fluid malignant cells or known brain metastases or with a history of cerebrospinal fluid malignant cells or brain metastases.
• History or presence of non-malignant CNS disorder, such as seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement.
• Subjects with cardiac atrial or cardiac ventricular lymphoma involvement.
• History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, New York Heart Association Class II or greater congestive heart failure, or other clinically significant cardiac disease within 12 months of enrollment.
• Requirement for urgent therapy due to tumor mass effects, such as bowel obstruction or blood vessel compression.