Table 2.

Study design characteristics and eligibility criteria for TRANSCEND and JULIET

	TRANSCEND (liso-cel) [6]	JULIET (tisagenlecleucel) [8]
Key study design features
Phase	1	2
Design	Single arm	Single arm
Blinding	Open label	Open label
Centers	Multicenter	Multicenter
Country	US	Multiple (US, Canada, Europe, Japan)
Bridging therapy	Allowed	Allowed
PET-positive disease after bridging therapy	Confirmed	Not always confirmed
Lymphodepleting chemotherapy	Yes	Yes (omitted if white blood cell count ≤ 1000 cells/μL)
Regimen and dosage of lymphodepleting chemotherapy	Fludarabine (30 mg/m2/day for 3 days) and cyclophosphamide (300 mg/m2/day for 3 days), completed 2‒7 days before infusion	Fludarabine (25 mg/m2 IV daily for 3 days) and cyclophosphamide (250 mg/m2 IV daily for 3 days, starting with the first dose of fludarabine) within 1 week before infusion Alternatively, bendamustine 90 mg/m2 IV daily for 2 daysa
CAR T-cell regimen and dosage	Dose level 1, single-dose regimen: 50 × 106 CAR+ T cells (25 × 106 CD8+ CAR+ T cells and 25 × 106 CD4+ CAR+ T cells) Dose level 1, two-dose regimen: 50 × 106 CAR+ T cells Dose level 2, single-dose regimen: 100 × 106 CAR+ T cells (50 × 106 CD8+ CAR+ T cells and 50 × 106 CD4+ CAR+ T cells) Dose level 3, single-dose regimen: 150 × 106 CAR+ T cells (75 × 106 CD8+ CAR+ T cells and 75 × 106 CD4+ CAR+ T cells)	Single infusion of 1 to 5 × 108 CAR+ T cells

	TRANSCEND (liso-cel) [6]	JULIET (tisagenlecleucel) [8]	Action taken for TRANSCEND IPD and rationale
Key inclusion criteria
NHL subtype	DLBCL NOS, HGBCL, tFL, tiNHL, PMBCL, FL3B	DLBCL NOS, HGBCL, tFL	Recategorized TRANSCEND and JULIET to improve comparability of patients with DLBCL. For TRANSCEND, DLBCL NOS, HGBCL, and tiNHL were combined as “DLBCL”. For JULIET, DLBCL NOS, HGBCL, and other were combined into “DLBCL”
Age	≥ 18 years	≥ 18 years	None
ECOG PS	≤ 2b	≤ 1	None
Prior lines of treatment	≥ 2	≥ 2	Redefined in TRANSCEND such that a line of therapy included chemotherapy, auto-HSCT, allo-HSCT, and radiotherapy to align with JULIET definition
Prior auto-HSCT	Allowed	Allowed	None
Prior regimen required	Anthracycline and rituximab (or other CD20-targeted agents)	Included rituximab and anthracycline	None
Response to prior therapy	R/R disease after ≥ 2 lines of therapy or after auto-HSCT	R/R disease after ≥ 2 lines of chemotherapy, including rituximab and anthracycline Patients had to have either failed auto-HSCT, be ineligible for, or not consent to auto-HSCT	None
Absolute lymphocyte count	No minimum requirementc	≥ 300/μL	Redefined in TRANSCEND to align with JULIET definition
Absolute neutrophil count	No minimum requirementc	> 1000/μL	None
Platelet count	No minimum requirementc	≥ 50,000/μL	None
Hemoglobin	No minimum requirementc	> 8.0 g/dL	None
Alanine aminotransferase	≤ 5 × ULN	≤ 5 × ULN for age	None
Total bilirubin	< 2.0 mg/dL	≤ 2.0 × ULN	None
Serum creatinine	≤ 1.5 × ULN	≤ 1.5 × ULN	None
CrCl	> 30 mL/min/1.73 m2 (Cockcroft-Gault)	≥ 60 mL/min/1.73 m2	Redefined in TRANSCEND to align with JULIET definition
Dyspnea	Grade ≤ 1 by NCI CTCAE	Grade ≤ 1	None
Oxygen saturation	≥ 92% on room air	> 91% on room air	None
LVEF	≥ 40%	≥ 45%	Redefined in TRANSCEND to align with JULIET definition
Tumor burden	SPD (cm2) measured before lymphodepleting chemotherapy and at enrollment	Reported as tumor volume (mL)	No action was taken as variables were not compatible between studies (i.e., measured differently); therefore, would not be included in any subsequent analyses
Bulky disease	Single nodal mass of ≥ 10 cm by CT based on Lugano classification	NR	No action taken as variables were not compatible between studies; therefore, would not be included in any subsequent analyses
Key exclusion criteria
Prior allo-HSCT	Allowed (not within 90 days of leukapheresis)	Not allowed	None
Active CNS lymphoma	Secondary CNS lymphoma allowed	Not allowed	None
History of other primary malignancy	Not allowed unless other primary malignancy was in remission for ≥ 2 years	Not allowed unless primary malignancy, which had been completely resected and was in complete remission for ≥ 5 years	None
Infections	Uncontrolled systemic fungal, bacterial, viral, or other infection despite appropriate antibiotics or other treatment at the time of leukapheresis or liso-cel administration	Uncontrolled acute life-threatening bacterial, viral, or fungal infection (i.e., blood culture positive ≤ 72 h before infusion)	None
Cardiovascular conditions or clinically significant cardiac disease	Within 6 months of screening/enrollment	Myocardial infarction within 6 months of screening Cardiac arrhythmia not controlled with medical management	None

allo-HSCT allogeneic hematopoietic stem cell transplantation, auto-HSCT autologous hematopoietic stem cell transplantation, CAR chimeric antigen receptor, CNS central nervous system, CrCl creatinine clearance, CT computed tomography, DLBCL diffuse large B-cell lymphoma, ECOG PS Eastern Cooperative Oncology Group performance status, FL3B follicular lymphoma grade 3B, HGBCL high-grade B-cell lymphoma, IPD individual patient data, IV intravenous, liso-cel lisocabtagene maraleucel, LVEF left ventricular ejection fraction, NCI CTCAE National Cancer Institute Common Terminology Criteria for Adverse Events, NHL non-Hodgkin lymphoma, NOS not otherwise specified, NR not reached, PET positron emission tomography, PMBCL primary mediastinal B-cell lymphoma, R/R relapsed or refractory, SPD sum of the product of perpendicular diameters, tFL transformed follicular lymphoma, tiNHL transformed indolent non-Hodgkin lymphoma, ULN upper limit of normal

^aBendamustine regimen was used if there was previous grade 4 hemorrhagic cystitis with cyclophosphamide or the patient demonstrated resistance to a previous cyclophosphamide-containing regimen. Of patients in the JULIET efficacy analysis set (n = 93), 68 received fludarabine and cyclophosphamide, 18 received bendamustine, and 8 received no lymphodepleting chemotherapy

^bECOG PS of 2 was allowed until Protocol Amendment 5, August 17, 2017 to align with the eligibility criteria in Abramson et al. [37]

^cAssessed by the investigator to have had adequate bone marrow function to receive lymphodepleting chemotherapy