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Table 2 Study design characteristics and eligibility criteria for TRANSCEND and JULIET

From: Matching-adjusted indirect treatment comparison of chimeric antigen receptor T-cell therapies for third-line or later treatment of relapsed or refractory large B-cell lymphoma: lisocabtagene maraleucel versus tisagenlecleucel

 

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

  1. 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
  2. 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
  3. bECOG PS of 2 was allowed until Protocol Amendment 5, August 17, 2017 to align with the eligibility criteria in Abramson et al. [37]
  4. cAssessed by the investigator to have had adequate bone marrow function to receive lymphodepleting chemotherapy