Main trials in single antigen–targeted CAR T cells for B-NHL
| Reference . | Trial phase . | CAR construct . | n∗ (age range) and diagnoses . | In vivo expansion . | Best ORR and CR . | Toxicity . | Persistence . | Relapse incidence and phenotype . | EFS/OS . |
|---|---|---|---|---|---|---|---|---|---|
| B-NHL CD19 | |||||||||
| Neelapu et al, 201713 (ZUMA-1) | 2 | Axicabtagene ciloleucel CD19 scFv – CD28 – CD3z | 101 (25-76 y)
| Peak at 14 d (peak 10-100 copies per μL) | ORR: 82/101 (82%) CR: 54/101 (54%) | CRS G3/4: 13/101 (13%) NTx G3/4/5: 28/101 (28%)† | Most patients with detectable CAR T cells at 180 d | 58/101 (58%) 11 patients available CD19-status: 7/11 CD19+ disease 3/11 had CD19– disease | Median PFS 5.8 mo 41% PFS at 15 mo OS 52% at 18 mo |
| Abramson et al, 202018 (TRANSCEND) | 2 | Lisocabtagene maraleucel CD19 scFv – 4-1BB – CD3z (sequential CD8+ then CD4+ components at equal doses) | 268 (18-86 y)
| Peak at 12 d (Cmax 23 928 copies per μL) | ORR: 186/256 (73%) CR: 136/256 (53%) | CRS G3/4: 6/268 (2%) NTx G3/4/5: 27/268 (10%)† | CAR T cells detectable at 1 y in 35/67 patients (52%) B-cell aplasia at 1 y in 51/70 (73%) | NR | Median PFS 6.8 mo 44% PFS at 12 mo Median OS 21.1 mo |
| Schuster et al, 201914 (JULIET) | 2 | Tisa-cel CD19 scFv – 4-1BB – CD3z | 93 (22-76 y)
| Peak at 9 d (Cmax 5530 copies per μg) | ORR: 48/93 (52%) CR: 37/93 (40%) | CRS G3/4: 24/93 (22%) NTx G3/4/5: 13/93 (14%)† | Not quantified. Long-term persistence up to 2 y observed. | NR | PFS 65% at 12 mo |
| B-NHL – CD20 | |||||||||
| Till et al, 201219 | 1 | CD20 scFv – CD28-4-1BB-CD3z Third-generation CAR | 4 Indolent lymphomas | 1 patient no expansion | 2 patients no evaluable disease 1 partial response | No grade 3/4 toxicities | 9-12 mo detectable CAR T cells | 1 progression after partial response | NR |
| Wang et al, 201420 | 1 | CD20 scFv – 4-1BB – CD3z | 7 (37-85 y) DLBCL | — | 1/7 CR 4/7 PR | CRS G3/4: 1 No NTx Reported delayed-onset CRS and toxicities in tumor involvement sites | NR | NR | NR |
| Zhang et al, 201621 | 2 | CD20 scFv – 4-1BB – CD3z | 11 | Peak levels at 4 wk (range, 800-255 044 copies per μg DNA) | Objective response rate: 9/11 (82%) CR: 6/11 (55%) PR: 3/11 (27%) | No CRS or NTx Excluded patients with intrapulmonary involvement, GI involvement, or refractory to debulking therapy | NR | Relapse incidence: 6/11 All with loss of persistence and recovery of CD20+ B-cells | Median PFS 6 mo |
| B-NHL – CD22 | |||||||||
| Baird et al, 202122 | 1 | CD22 scFv (m971) – 4-1BB – CD3z | 3 | Peak levels at 14 d | CR 3/3 at 6 mo | CRS G3/4: 0/3 NTx G3/4: 0/3 | 3/3 detectable at last assessment at 6 mo | No relapses at 6 mo | NR |
| Reference . | Trial phase . | CAR construct . | n∗ (age range) and diagnoses . | In vivo expansion . | Best ORR and CR . | Toxicity . | Persistence . | Relapse incidence and phenotype . | EFS/OS . |
|---|---|---|---|---|---|---|---|---|---|
| B-NHL CD19 | |||||||||
| Neelapu et al, 201713 (ZUMA-1) | 2 | Axicabtagene ciloleucel CD19 scFv – CD28 – CD3z | 101 (25-76 y)
| Peak at 14 d (peak 10-100 copies per μL) | ORR: 82/101 (82%) CR: 54/101 (54%) | CRS G3/4: 13/101 (13%) NTx G3/4/5: 28/101 (28%)† | Most patients with detectable CAR T cells at 180 d | 58/101 (58%) 11 patients available CD19-status: 7/11 CD19+ disease 3/11 had CD19– disease | Median PFS 5.8 mo 41% PFS at 15 mo OS 52% at 18 mo |
| Abramson et al, 202018 (TRANSCEND) | 2 | Lisocabtagene maraleucel CD19 scFv – 4-1BB – CD3z (sequential CD8+ then CD4+ components at equal doses) | 268 (18-86 y)
| Peak at 12 d (Cmax 23 928 copies per μL) | ORR: 186/256 (73%) CR: 136/256 (53%) | CRS G3/4: 6/268 (2%) NTx G3/4/5: 27/268 (10%)† | CAR T cells detectable at 1 y in 35/67 patients (52%) B-cell aplasia at 1 y in 51/70 (73%) | NR | Median PFS 6.8 mo 44% PFS at 12 mo Median OS 21.1 mo |
| Schuster et al, 201914 (JULIET) | 2 | Tisa-cel CD19 scFv – 4-1BB – CD3z | 93 (22-76 y)
| Peak at 9 d (Cmax 5530 copies per μg) | ORR: 48/93 (52%) CR: 37/93 (40%) | CRS G3/4: 24/93 (22%) NTx G3/4/5: 13/93 (14%)† | Not quantified. Long-term persistence up to 2 y observed. | NR | PFS 65% at 12 mo |
| B-NHL – CD20 | |||||||||
| Till et al, 201219 | 1 | CD20 scFv – CD28-4-1BB-CD3z Third-generation CAR | 4 Indolent lymphomas | 1 patient no expansion | 2 patients no evaluable disease 1 partial response | No grade 3/4 toxicities | 9-12 mo detectable CAR T cells | 1 progression after partial response | NR |
| Wang et al, 201420 | 1 | CD20 scFv – 4-1BB – CD3z | 7 (37-85 y) DLBCL | — | 1/7 CR 4/7 PR | CRS G3/4: 1 No NTx Reported delayed-onset CRS and toxicities in tumor involvement sites | NR | NR | NR |
| Zhang et al, 201621 | 2 | CD20 scFv – 4-1BB – CD3z | 11 | Peak levels at 4 wk (range, 800-255 044 copies per μg DNA) | Objective response rate: 9/11 (82%) CR: 6/11 (55%) PR: 3/11 (27%) | No CRS or NTx Excluded patients with intrapulmonary involvement, GI involvement, or refractory to debulking therapy | NR | Relapse incidence: 6/11 All with loss of persistence and recovery of CD20+ B-cells | Median PFS 6 mo |
| B-NHL – CD22 | |||||||||
| Baird et al, 202122 | 1 | CD22 scFv (m971) – 4-1BB – CD3z | 3 | Peak levels at 14 d | CR 3/3 at 6 mo | CRS G3/4: 0/3 NTx G3/4: 0/3 | 3/3 detectable at last assessment at 6 mo | No relapses at 6 mo | NR |
Cmax, peak serum concentration; CR, complete remission; CRS, cytokine release syndrome; DLBCL NOS, diffuse large B-cell lymphoma not otherwise specified; GI, gastrointestinal; HGBCL, high-grade B-cell lymphoma; NR, not reported; NTx, neurotoxicity; ORR, objective response rate; OS, overall survival; PFS, progression-free survival; PMBCL, primary mediastinal B-cell lymphoma; PR, partial response; tFL, transformed follicular lymphoma; t iNHL, DLBCL transformed from indolent non-Hodgkin lymphoma other than follicular lymphoma.
Showing the final number of patients who received infusions.
Used American Society for Transplantation and Cellular Therapy consensus criteria for CRS grading and Common Terminology Criteria for Adverse Events grading for neurotoxicity.