Relmacabtagene Autoleucel as First-Line Therapy for High-Risk Large B-Cell Lymphoma

Inclusion Criteria:

1. ≥ 18 years old;
2. Sign on the informed consent;
3. Histologically confirmed large B-cell lymphoma that also meets the definition ofhigh-risk large B-cell lymphoma as a lymphoma International Prognostic Index (IPI)score of 3-5 and/or high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6rearrangement (double/triple-hit lymphoma) (DHL/THL) and must be treated with 2 cyclesof CD20 monoclonal antibodies combined with anthracyclines. Presence of positive PETassessable lesions (DS score of 4 or 5) as determined by the Lugano criteria (Chesonet al., 2014)；
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
5. Expected survival greater than 12 weeks；
6. Adequate organ function：
7. Absolute neutrophil count ≥ 1000/μL；Absolute lymphocyte count ≥ 100/μL； Plateletcount ≥ 75,000/μL；Hb ≥ 80g/L；
8. Serum creatinine ≤ 1.5 × upper limit of normal (ULN) or creatinine clearance (Cockcroft-Gault formula) > 50 mL/min (serum creatinine clearance due to lymphomamass compression should be > 30 mL/min)；
9. Serum alanine aminotransferase (ALT) ≤ 5 upper limit of normal (ULN) and totalbilirubin ≤2ULN（or for subjects with Gilbert's syndrome or lymphoma invading theliver < 3 ULN）；
10. Baseline oxygen saturation > 92% on room air；
11. Left ventricular ejection fraction (LVEF) ≥50% assessed by echocardiography orradionuclide activity angiography (MUGA) within 1 month of enrollment；
12. Adequate vascular access for leukapheresis procedure;
13. Women of childbearing potential must agree to use highly effective methods ofcontraception for at least 28 days prior to lymphocyte clearance chemotherapy through 1 year after Relmacabtagene Autoleucel infusion; Males who have partners ofchildbearing potential must agree to use an effective barrier contraceptive method for 1 year after Relmacabtagene Autoleucel infusion.

Exclusion Criteria:

1. Lymphoma involving the central nervous system (CNS)；
2. History of another primary malignancy that has not been in remission for at least 2years;
3. History of Richter's transformation of chronic lymphocytic leukemia or primarymediastinal B-cell lymphoma；
4. Subjects has HBV, HCV, HIV or syphilis infection at the time of screening;
5. Deep venous thrombosis (DVT)/Pulmonary embolism (PE), or DVT/PE requiresanti-coagulation within 3 months prior to signing the ICF;
6. Subjects with uncontrolled systemic fungal, bacterial, viral or other infection;
7. Presence of acute or chronic graft-versus-host disease (GVHD);
8. History of any serious cardiovascular disease or presence of clinically relevant CNSpathology;
9. Pregnant or nursing women;
10. Subjects Received an autologous or allogeneic hematopoietic stem cell transplant；
11. Uncontrolled conditions or unwillingness or inability to follow the proceduresrequired in the protocol;
12. Received CAR T-cell or other genetically-modified T-cell therapy previously；
13. Received live vaccination within 6 weeks prior to lymphocyte clearance chemotherapy；
14. History of severe hypersensitivity reactions to any of the drug ingredients used inthis study product.