Table 1.
Summary of CD19 CAR-T cell therapy clinical trials for relapsed or refractory adult ALL.
AE adverse event, CAR chimeric antigen receptor, CR complete remission, CRS cytokine release syndrome, Cy cyclophosphamide, FC flow cytometry, FHCRC Fred Hutchinson Cancer Research Center, Flu fludarabine; Hebei Yanda Lu Daopei Hospital, ICANS immune effector cell-associated neurotoxicity syndrome, MFC multiparameter flow cytometry; MSKCC Memorial Sloan Kettering Cancer Center, MOF multiorgan failure, MRD minimal residual disease.
| Institution | Multicenter10 | UPENN11 | FHCRC3 | MSKCC7 | Multicenter24 | HYLDH4 |
|---|---|---|---|---|---|---|
| Trial identification | ZUMA-3 NCT02614066 |
NCT01029366
NCT02030847 |
FH2639 NCT01865617 |
NCT01044069 | ROCKET NCT02535364 |
ChiCTR-IIh-16008711 |
| Number of subjects infused | 45 | 35 | 53 | 53 | 32 | 42 including both children and adults |
| CAR T-cell product | KTE-X19 (brexucabtagene autoleucel) | CTL019 (tisagenlecleucel) | JCAR014 | 19-28z | JCAR015 | Not reported |
| Co-stimulatory domain | 19-28z | 4-1BB | 4-1BB | CD28 | CD28 | 4-1BB |
| scFv | FMC63 | FMC63 | FMC63 | SJ25C1 | SJ25C1 | Not reported |
| CAR T-cell dose | 0.5 x106/kg 1 x 106/kg 2 x 106/kg |
5x108 total dose
(single) 5x107 (single or fractionated*) 5x108 (fractionated*) |
2 x105/kg 2 x106/kg 6 2 x 107/kg |
1 x 106/kg 3 x 106/kg |
1 x106/kg 3 x106/kg |
0.05-1.6x106/kg |
| Lymphodepletion | Cy 900mg/m2x1 + Flu 25mg/m2x3 | Cy 300 mg/m2 every 12 hours x3,
71% Cy 500 mg/m2 x2 + Flu 30 mg/m2 x4, 29% |
Cy 60mg/kg x1 + Flu 25mg/m2x3,
45% Cy 300mg/m2 x1 + Flu 30mg/m2x3, 45%, 21% |
Cy 3g/m2, 71% Cy + Flu 19% |
Cy 1-3g/m2 x1 Cy 30-60mg/kg x1+Flu 25mg/m2x3 |
Cy 250mg/m2x3 + Flu 30mg/m2x3 |
| Median BM blasts prior to lymphodepletion | 59% | >5% in 94% | 28% | 63% | ≥5% in 100% | 32.6% |
| MRD negative CR by MFC | 75% | Overall 69% 90% in 5x108 fractionated cohort |
85% | 67% | 55% | 85% |
| Median CRS duration (days) | Not reported | Not reported | 3 | Not reported | Not reported | Not reported |
| Median ICANS duration (days) | Original AE management,
20.5 Revised AE management, 11 |
Not reported | 5 | Not reported | Not reported | Not reported |
| Seizures (n) | 0 | Not reported | 3 | Not reported | Not reported | 8 |
| Cerebral edema (n) | 0 | 0 | 1 | 0 | 5 | Not reported |
| Deaths attributed to CAR-T cell therapy (n) | 2 (4%) | 3 (8%) | 2 (4%) | 1 (2%) | 5 (16%) | 2 |
| Causes of death | Severe CRS with MOF Cerebral infarction |
Refractory hypotension in the context of
sepsis and CRS Intracranial hemorrhage |
Cerebral edema Severe CRS with MOF |
Severe CRS with MOF | Cerebral edema | Intracranial hemorrhage Heart failure |
a
Fractionated dosing: day 1, 10%; day 2, 30%; day 3, 60%.