Trial design features
| . | ZUMA-7 . | Belinda . | Transform . |
|---|---|---|---|
| Histologies included | DLBCL NOS,* including transformed from FL, HGBCL with or without MYC and BCL2/6, T/H-RLBCL, Primary cutaneous DLBCL - leg type | DLBCL NOS, including transformed from indolent NHL, HGBCL with or without MYC and BCL2/6, T/H-RLBCL, Primary cutaneous DLBCL - leg type FL grade 3B, PMBCL, Intravascular LBCL, ALK + LBCL, HHV8 + LBCL | DLBCL NOS, including transformed from indolent NHL, HGBCL with MYC and BCL2/6, T/H-RLBCL, FL grade 3B, PMBCL |
| Product | Axi-cel, CD28/CD3zeta 2 × 106 cells/kg | Tisa-cel, 4 – 1BB/CD3zeta 0.6-6 × 108 cells | Liso-cel, 4 − 1BB/CD3zeta 1 × 108 cells |
| 1L refractory definition | • PD as best response • SD after at least 4 cycles • PR with + biopsy or PD <12 mo from 1L start | • PD/SD as best response | • PD/SD/PR as best response • CR with progression <3 mo |
| 1L relapsed definition | • CR followed by + biopsy <12 mo from 1L end | • Positive biopsy ≤12 mo from 1L end | • CR followed by + biopsy 3-12 mo from 1L end |
| Age | 18+ | 18+ | 18-75 |
| Leukapheresis time point | • At randomization • Only CAR T-cell arm | • Before randomization • All patients | • Before randomization • All patients |
| Stratification factors | 1. Refractory vs Relapse ≤6 mo vs Relapse >6-12 mo 2. 2L AAIPI 0-1 vs 2-3 | 1. Refractory or relapsed ≤6 mo vs relapsed 6-12 mo 2. IPI <2 vs ≥2 | 1. Refractory vs relapse 2. 2L AAIPI 0-1 vs 2-3 |
| Bridging therapy | • Dexamethasone ≤40 mg for ≤4 d | • R-ICE • R-GDP • R-DHAP • R-GemOx | • R-ICE • R-GDP • R-DHAP |
| LD chemotherapy | • Fludarabine 30 mg/m2 × 3 d • Cyclophosphamide 500 mg/m2 × 3 d | • Fludarabine 25 mg/m2 × 3 d and • Cyclophosphamide 250 mg/m2 × 3d OR • Bendamustine 90 mg/m2 × 2 d | • Fludarabine 30 mg/m2 × 3 d • Cyclophosphamide 300 mg/m2 × 3 d |
| SOC chemotherapy | • R-ICE • R-GDP • R-DHAP • R-ESHAP | • R-ICE • R-GDP • R-DHAP • R-GemOx | • R-ICE • R-GDP • R-DHAP |
| Crossover to CAR T-cell therapy | No | Yes, if • <PR/CR by 12 wk (after 2 SOC regimens) • PD at any time | Yes, if • <PR/CR by 9 wk • PD at any time • Need for new therapy after 18 wk |
| EFS definition | Time from randomization to: • PD • Death • <PR at day 150 assessment • Start of new lymphoma therapy | Time from randomization to: • PD • Death • <PR at/after week 12 | Time from randomization to: • PD • Death • ≤PR by week 9 • Start of new lymphoma therapy |
| . | ZUMA-7 . | Belinda . | Transform . |
|---|---|---|---|
| Histologies included | DLBCL NOS,* including transformed from FL, HGBCL with or without MYC and BCL2/6, T/H-RLBCL, Primary cutaneous DLBCL - leg type | DLBCL NOS, including transformed from indolent NHL, HGBCL with or without MYC and BCL2/6, T/H-RLBCL, Primary cutaneous DLBCL - leg type FL grade 3B, PMBCL, Intravascular LBCL, ALK + LBCL, HHV8 + LBCL | DLBCL NOS, including transformed from indolent NHL, HGBCL with MYC and BCL2/6, T/H-RLBCL, FL grade 3B, PMBCL |
| Product | Axi-cel, CD28/CD3zeta 2 × 106 cells/kg | Tisa-cel, 4 – 1BB/CD3zeta 0.6-6 × 108 cells | Liso-cel, 4 − 1BB/CD3zeta 1 × 108 cells |
| 1L refractory definition | • PD as best response • SD after at least 4 cycles • PR with + biopsy or PD <12 mo from 1L start | • PD/SD as best response | • PD/SD/PR as best response • CR with progression <3 mo |
| 1L relapsed definition | • CR followed by + biopsy <12 mo from 1L end | • Positive biopsy ≤12 mo from 1L end | • CR followed by + biopsy 3-12 mo from 1L end |
| Age | 18+ | 18+ | 18-75 |
| Leukapheresis time point | • At randomization • Only CAR T-cell arm | • Before randomization • All patients | • Before randomization • All patients |
| Stratification factors | 1. Refractory vs Relapse ≤6 mo vs Relapse >6-12 mo 2. 2L AAIPI 0-1 vs 2-3 | 1. Refractory or relapsed ≤6 mo vs relapsed 6-12 mo 2. IPI <2 vs ≥2 | 1. Refractory vs relapse 2. 2L AAIPI 0-1 vs 2-3 |
| Bridging therapy | • Dexamethasone ≤40 mg for ≤4 d | • R-ICE • R-GDP • R-DHAP • R-GemOx | • R-ICE • R-GDP • R-DHAP |
| LD chemotherapy | • Fludarabine 30 mg/m2 × 3 d • Cyclophosphamide 500 mg/m2 × 3 d | • Fludarabine 25 mg/m2 × 3 d and • Cyclophosphamide 250 mg/m2 × 3d OR • Bendamustine 90 mg/m2 × 2 d | • Fludarabine 30 mg/m2 × 3 d • Cyclophosphamide 300 mg/m2 × 3 d |
| SOC chemotherapy | • R-ICE • R-GDP • R-DHAP • R-ESHAP | • R-ICE • R-GDP • R-DHAP • R-GemOx | • R-ICE • R-GDP • R-DHAP |
| Crossover to CAR T-cell therapy | No | Yes, if • <PR/CR by 12 wk (after 2 SOC regimens) • PD at any time | Yes, if • <PR/CR by 9 wk • PD at any time • Need for new therapy after 18 wk |
| EFS definition | Time from randomization to: • PD • Death • <PR at day 150 assessment • Start of new lymphoma therapy | Time from randomization to: • PD • Death • <PR at/after week 12 | Time from randomization to: • PD • Death • ≤PR by week 9 • Start of new lymphoma therapy |
1L, first-line; 2L, second-line; AAIPI, age-adjusted international prognostic index; ALK, anaplastic lymphoma kinase; BCL2/6, B-cell lypmphoma protein 2 and/or 6; FL, follicular lymphoma; HGBCL, high-grade B-cell lymphoma; HHV8, human herpesvirus-8; IPI, international prognostic index; LD, lymphodepleting chemotherapy; PD, progressive disease; PMBCL, primary mediastinal B-cell lymphoma; PR, partial response; R-ESHAP, rituximab, etoposide, steroids, high-dose cytarabine, cisplatin; R-GemOx, rituximab, gemcitabine, oxaliplatin; SD, stable disease; SOC, standard of care; T/H-RLBCL, T-cell/histiocyte-rich large B-cell lymphoma.
The ZUMA7 protocol does not specifically state LBCL subtypes, but the subtypes listed are included in patients enrolled.