Table 1.
Overview of the main clinical studies investigating CD19- or CD22-targeted CAR-T in paediatric patients and AYA with BCP-ALL.
| Research group, trial phase | References | Patients, N | Prior HSCT, n (%) | Overall response rate (within 3 months) | Efficacy (beyond 3 months) | CAR-T cell persistence | ALL-targeted interventions post CART* |
|---|---|---|---|---|---|---|---|
| Tisagenlecleucel, phase I/II studies | |||||||
| CHOP, I/IIa | (22) | 30 (25 P+AYA) | 18 (60%) | 90% (27/30) at 1 mo. | 6-mo. EFS: 67% 6-mo. OS: 78% |
6-mo. persistence: 68% | 3 HSCT (11%†), 1 DLI, 1 re-infusion |
| CHOP, I/IIa | (23) | 59 (P+AYA) | 39 (61%) | 93% (55/59) at 1 mo. | 6-mo. RFS: 76% 12-mo. RFS: 55% 12-mo. OS: 79% |
Unknown | 5 HSCT (9%†), 1 DLI, 17 re-infusion |
| ELIANA, II | (12) | 75 (P+AYA) | 46 (61%) | 81% (61/75) at 3 mo. | 6-mo. EFS: 73% 12-mo. EFS: 50% 12-mo. OS: 76% |
6-mo persistence: 83% Median persistence: 168 days | 8 HSCT (13%†), 4 huCART19, 1 ponatinib, 1 vincristine and blinatumomab, 1 ATG |
| Tisagenlecleucel, real-world experience | |||||||
| CIBMTR, retrospective | (24) | 255 (0.4–26 yrs) | 71 (28%) | 86% (213/249) at 3 mo. | 6-mo DoR: 78% 6-mo OS: 89% |
Unknown | 34 HSCT (16%†) |
| CD19 CAR-T other than tisagenlecleucel | |||||||
| CARPALL, II | (25) | 14 (P+AYA) | 10 (71%) | 86% (12/14) at 3 mo. | 1-yr EFS: 46% 1-yr OS: 63% |
Median persistence: 215 days | 0 HSCT |
| Seattle, I | (26) | 45 (P) | 28 (62%) | 93% (40/43) at Day 21 | 12-mo. EFS: 50% 12-mo. OS: 66% |
Median duration: 3 mo. | 11 HSCT (28%†), 10 re-infusions |
| NCI, I | (18, 27) | 20 (P+AYA) | 7 (35%) | 70% (14/20) at Day 28 | OS: 52% (Median FU 10 mo.) | Maximum persistence: 68 days | 10 HSCT (71%†), 3 re-infusions |
| MSKCC, I | (16) | 25 (P+AYA) | 18 (75%) | 75% (18/24) at Day 28 | Dependent on LD/ cell dose | Median persistence: 7 days | 15 HSCT (83%†) |
| Sheba, Ib/II | (17) | 20 (18 P+AYA) | 10 (50%) | 90% (18/20) at Day 28 | 1-yr EFS: 73% 1-yr OS: 90% |
Median persistence 23 days | 14 HSCT (77%†) |
| Barcelona, I | (28) | 38 (19 P+AYA) | 33 (87%) | 84% (32/38) at Day 28 | P: 1-yr DFS 82% P: 1-yr OS 78% |
P: BCA at 1 yr: 48% | NR |
| CD22 CAR-T | |||||||
| NCI, I | (29) | 21 (P+AYA) | 21 (100%) | Dependent on cell dose | Relapse: 8/12 responders | Maximum persistence: 18 mo. | None |
| NCI, I | (30) | 58 (55 ALL P+AYA) | 39 (67%) | 72% (40/55 ALL) at Day 28 | Median OS: 13.4 mo. Median RFS: 6.0 mo. | Unknown | 13 HSCT (33%†; 100% of MRD-negative patients), 1 re-infusion |
While still in CR.
Out of those patients who responded (CR).
ATG, anti-thymocyte globulin; AYA, adolescent and young adult; BCA, B-cell aplasia; BCP-ALL, B-cell precursor acute lymphoblastic leukaemia; CAR-T, chimeric antigen receptor T-cell therapy; CHOP, Children's Hospital of Philadelphia; CIBMTR, Centre for International Blood and Marrow Transplant Research; DLI, donor lymphocyte infusion; DoR, duration of response; DFS, disease-free survival; EFS, event-free survival; FU, Follow-up; HSCT, haematopoietic stem cell transplantation; huCART19, human CD19 CAR-T; LD, Lymphodepletion; LFS, leukaemia-free survival; MSKCC, Memorial Sloan Kettering Cancer Centre; mo., month; OS, overall survival; NCI, National Cancer Institute; NR, not reported; P, paediatric; RFS, relapse-free survival; yr, year.