Table 1.
A list of major anti-CD19 CAR-T cell therapy trials.
| CD19-positive B-cell malignancy | n | LD chemotherapy | Adverse effect | Long-term EFS | PFS | CAR-T cell dose/kg | OS | Outcome | Best response duration | Ref. |
|---|---|---|---|---|---|---|---|---|---|---|
| FL | 2 | FLU (post T-cell infusion) | Lymphopenia | ND | ND | 100–200 × 107/m2 total T cells | ND | No responses | ND | 25 |
| CLL, ALL |
9 | None or (CTX) | B cell aplasia, fever, hypotension, death | ND | ND | 0.4–3 × 107 | 1 PR, 2 SD, 1 CR, 4 NR, 1 death | PR up to 12 week | 26 | |
| NHL, CLL, SMZL |
8 | CTX, FLU | B cell aplasia, CRS | ND | ND | 0.3–3 × 107 | 6 PR, 1 CR, 1 NE The total SOFA: serum IFNγ and serum TNF levels versus time (P = 0.02 for IFNγ and P = 0.001 for TNF |
CR > 18 months | 27 | |
| CLL | 14 | CTX, FLU | B cell aplasia, CRS, TLS, neutropenia |
ND | 18-month PFS 28.6% | 1.4–113 × 107 | 29 months; 18-month, OS 71% | 4 CR, 4 PR The peak value of CTL019 was statistically associated with response (P = 0.008), higher peak expansion of CTL019 associated with CRS, and CRS was associated with clinical response (P < 0.05) |
CR up to 53 months | 28, 29 |
| ALL | 16 | CTX | Severe CRS | ND | ND | 0.14–0.3 × 107 | 14 CR, 12 MRD The threshold where patients are at high risk for clinical complications secondary to sCRS. ∗P < 0.05, unpaired t tests at the corresponding time point. Specific P values for the time points are as follows: Day 2, P = 0.035 (n = 13); Day 4, P = 0.025 (n = 12); Day 5, P = 0.019 (n = 11); and Day 9, P = 0.01 (n = 8). |
CR up to 3 months | 30, 31 | |
| CLL, NHL |
20 | Allo-HSCT preparative regimen, DLI; none | B cell aplasia, CRS, hypotension, TLS |
39% at 6 months (Brundo et al.) | ND | 0.04–0.8 × 107 | 2 PR, 6 CR, 8 SD, 4 PD For CD4+ T cells, the difference in PD-1 expression between CAR+ cells and CAR– cells was statistically significant (P = 0.03) |
CR up to 30 months | 32, 33 | |
| ALL | 30 | None or VP/CTX | CRS, CNS toxicity | 67% at 6 months | ND | 0.2–1.2 × 107 | 6-month overall survival was 78% | 27 CR, 22 MRD Patients who had severe cytokine-release syndrome had higher peak levels of interleukin-6 (P < 0.001), higher peak levels of C-reactive protein (P = 0.02), ferritin (P = 0.005), interferon-γ (P < 0.001), and soluble interleukin-2 receptor (P < 0.001), patients with severe cytokine-release syndrome also had higher levels of CTL019-positive CD8 cells (P = 0.012) and CTL019-positive CD3 cells (P = 0.026). |
CR up to 24 months | 2, 34 |
| ALL, CLL |
8 | Allo-HSCT preparative regimen; none immediately before T-cell infusion | None | ND | ND | 1.9–11 × 107 | ND | 1 CR, 1 PR, 1 SD, 2 cCR, 3 NR | CR up to 3 months | 35 |
| DLBCL, PMBCL, follicular |
22 | CTX, FLU | Neurologic toxicities, myelodysplastic syndrome, vision loss |
ND | 12-month PFS 63.3% | 0.1–0.6 × 107 | ND | 4 PR, 12 CR, 4 PD, 2 SD There was an association between the percentage of central memory T cells among the infused CAR-T cells and peak blood CAR T-cell levels (P < 0.001; Spearman r = 0.7) |
CR > 24 months | 36 |
| ALL, NHL |
21 | CTX, FLU | CRS, B cell aplasia | 78.8% at 4.8 months | ND | 0.3–0.003 × 107, 2 × 107 |
51.6% at 9.7 months | 14 CR, 13 MRD The concentrations of CSF CD19-CAR T cells were higher in patients who developed neurotoxicity than in those who did not (P = 0·0039) |
CR up 19 months | 37 |
| NHL | 32 | CTX, FLU | Severe neurotoxicity, CRS | ND | ND | 2 × 105, 2 × 106, 2 × 107 EGFRt+cells/kg | 10 CR, 19 ORR of 30 evaluable | 38 | ||
| ALL | 45 | CTX, FLU | Severe neurotoxicity, CRS | 50.8% at 12 months | ND | 0,5 × 106, 1 × 106, 5 × 106, 10 × 106 EGFRt+cells/kg | 69.5% at 12 months | MRD-negative CR 93% There was no effect of dose level (P = 0.32), disease burden (P = 0.93), CD19 antigen load (P = 0.23), or fludarabine and cyclophosphamide lymphodepletion (P = 0.32) on the occurrence of severe neurotoxicity; however, the presence of severe CRS was predictive of subsequent severe neurotoxicity (P = 0.01) |
27 months | 39 |
| DLBCL | 7 | CTX, FLU | Severe neurotoxicity, CRS | ND | ND | 2 × 106 | ND | CR 57%, ORR 71% | 12 months | 40 |
cCR, continuous complete remission; CR, complete remission; CRS, cytokine release syndrome; CTX, cotrimoxazole; EFS, event free survival; FLU, fludarabine; HSCT, hematopoietic stem cell transplantation; LD, low dose; MRD, minimal residual disease; ND, not detected; NE, not evaluable; NR, no response; ORR, overall response rate; OS, overall survival; PD, progressive disease; PFS, progression-free survival; PR, partial remission; SD, stable disease.