Trials of CD19-directed CAR T-cell therapy involving older adults
| Reference . | T-cell engager . | Population . | Response . | Persistence/OS . |
|---|---|---|---|---|
| 20 | CD19 scFv/4-1BB CD3ζ | 32 enrolled, 30 infused (age 20-73 y; median 40 y) | CR: 91% (all enrolled), 97% (infused); MRD−: 84% (all enrolled), 90% (infused) | Addition of fludarabine increased persistence; 13/30 alive in CR (8 BMT, 5 no BMT); 13/30 BMT (8 alive, 5 died [2 relapse, 3 TRM]) |
| 46 | CD19 scFv/ CD28 CD3ζ | 26 enrolled, 20 infused | 4/5 ALL patients infused (MRD− CR) | 4/5 in CR with median follow-up 5 mo (range, 3-16 mo) |
| Adults (age 20-68 y; ALL median 25 y); cells collected from 13 sibling and 7 unrelated donors; 5 ALL patients | ||||
| 21 | CD19 scFv/4-1BB CD3ζ | 51 total: 42 relapsed/ refractory (age 3-68 y, median 11 y), 9 MRD+ (age 2-44 y, median 24 y) | 86% of RR patients CR/CRi, with 81% MRD− | 27/45 responding patients had BMT; 21/27 alive, median 133 d post-BMT; remainder no BMT; 9/18 relapsed |
| 100% of MRD+ patients became MRD− | ||||
| 22 | Humanized CD19 CAR/4- 1BB CD3-ζ/ T2A-EGFRt | 18 infused | First CAR T-cell infusion: 87% CR, 73% MRD−; 1/3 second CAR T-cell infusions MRD− CR | 6-m OS, 66% |
| 10 pediatric patients (age 3-15 y) | 4 patients underwent BMT (2 allogeneic, 2 autologous) | |||
| 8 adult patients (age 19-57 y) | ||||
| 3 failed murine CAR T-cell therapy | ||||
| 23 | CD19 scFv/4-1BB CD3ζ | Cohorts (median age 44 y, range 21-72 y) | ORR by cohort | Early abstract |
| 1-2: 6 patients, 5 × 107 | 1-2: 33% | |||
| 3: 6 patients, 5 × 108 | 3: 50% (3 died sepsis/CRS) | |||
| 4: 12 patients 5 × 108 (split doses) | 4: 83% (split dosing) | |||
| 24 | CD19 scFv/ CD28 CD3ζ | 83 enrolled, 53 infused | CR: 53% (all enrolled), 83% (infused); MRD−: 39% (all enrolled), 67% (infused) | Median EFS, 6.1 mo; median OS, 12.9 mo |
| Adult patients (age 23-74 y, median 44 y) | If CR and no BMT, 9/26 alive; if CR and BMT received, 5/17 alive |
| Reference . | T-cell engager . | Population . | Response . | Persistence/OS . |
|---|---|---|---|---|
| 20 | CD19 scFv/4-1BB CD3ζ | 32 enrolled, 30 infused (age 20-73 y; median 40 y) | CR: 91% (all enrolled), 97% (infused); MRD−: 84% (all enrolled), 90% (infused) | Addition of fludarabine increased persistence; 13/30 alive in CR (8 BMT, 5 no BMT); 13/30 BMT (8 alive, 5 died [2 relapse, 3 TRM]) |
| 46 | CD19 scFv/ CD28 CD3ζ | 26 enrolled, 20 infused | 4/5 ALL patients infused (MRD− CR) | 4/5 in CR with median follow-up 5 mo (range, 3-16 mo) |
| Adults (age 20-68 y; ALL median 25 y); cells collected from 13 sibling and 7 unrelated donors; 5 ALL patients | ||||
| 21 | CD19 scFv/4-1BB CD3ζ | 51 total: 42 relapsed/ refractory (age 3-68 y, median 11 y), 9 MRD+ (age 2-44 y, median 24 y) | 86% of RR patients CR/CRi, with 81% MRD− | 27/45 responding patients had BMT; 21/27 alive, median 133 d post-BMT; remainder no BMT; 9/18 relapsed |
| 100% of MRD+ patients became MRD− | ||||
| 22 | Humanized CD19 CAR/4- 1BB CD3-ζ/ T2A-EGFRt | 18 infused | First CAR T-cell infusion: 87% CR, 73% MRD−; 1/3 second CAR T-cell infusions MRD− CR | 6-m OS, 66% |
| 10 pediatric patients (age 3-15 y) | 4 patients underwent BMT (2 allogeneic, 2 autologous) | |||
| 8 adult patients (age 19-57 y) | ||||
| 3 failed murine CAR T-cell therapy | ||||
| 23 | CD19 scFv/4-1BB CD3ζ | Cohorts (median age 44 y, range 21-72 y) | ORR by cohort | Early abstract |
| 1-2: 6 patients, 5 × 107 | 1-2: 33% | |||
| 3: 6 patients, 5 × 108 | 3: 50% (3 died sepsis/CRS) | |||
| 4: 12 patients 5 × 108 (split doses) | 4: 83% (split dosing) | |||
| 24 | CD19 scFv/ CD28 CD3ζ | 83 enrolled, 53 infused | CR: 53% (all enrolled), 83% (infused); MRD−: 39% (all enrolled), 67% (infused) | Median EFS, 6.1 mo; median OS, 12.9 mo |
| Adult patients (age 23-74 y, median 44 y) | If CR and no BMT, 9/26 alive; if CR and BMT received, 5/17 alive |
BMT, bone marrow transplantation; CRS, cytokine release syndrome; ORR, overall response rate; OS, overall survival; TRM, treatment-related mortality.