Table 1 Clinical outcomes after CD19 CAR T cell therapy in patients with ALL. Data is collected from clinical trials for CD19 CAR T therapy in patients with ALL, primarily showing trials’ CAR T design and their outcomes including response rate, relapse rate and so on
study(reference) | CAR design | vector | patient population | conditioning regimen | CAR T cell dose | response,CR persistence | CAR T cell persistence | relapse rate | B cell aplasia time | CRS |
|---|---|---|---|---|---|---|---|---|---|---|
Cruz CR et al. [24] | FMC63-28ζ | gammaretrovirus | N=4, peds and adults, 18 y (9-40 y) | none | 1.5×107-1.2×108/m2,dose escalation | CR: 75% (3/4),3 mo (2-8 mo) | 8 w-12 w+ | overall: 33.3% (1/3);CD19+: 33.3% (1/3) | N/A | none |
Lee DW et al. [9] | FMC63-28ζ | gammaretrovirus | N=20, peds and young adults, 15 y (5-27 y) | FC | (0.03-3)×106/kg,dose escalation | CR: 70% (14/20),N/A | detectable up to 68 d | overall: 14.3% (2/14);CD19-: 14.3% (2/14) | 14-28 d | 28.6% (6/31) with Gr 3/4 CRS |
Kebriaei P et al. [23] | FMC63-28ζ | sleeping beauty | N=17, adults31 y (21-56 y) | N/A | 106-108/m2,dose escalation | CR: 64.7% (11/17), 6 mo (2-18 mo) | autologous: 201 d;allogeneic: 51 d | overall: 45.5% (5/11);CD19 expression not tested | N/A | none |
Jacoby E et al. [16] | FMC63-28ζ | gammaretrovirus | N=20, peds and adults, 11 y (5-48 y) | FC | 1 × 106/kg | CR: 90% (18/20), 28 d-21 mo,1-year EFS and OS rates were 73% and 90%, respectively | median: 23 d | overall: 22.2% (4/18);CD19+: 16.6% (3/18);CD19-: 5.6% (1/18) | N/A | 20% (4/20) with Gr 2/3 CRS |
Park JH et al. [12] | SJ25-28ζ | gammaretrovirus | N=53, adults, 44 y (23-74 y) | Cy | (1.5-3)×106/kg | CR: 83% (44/45),N/A, median EFS: 6.1 mo,median OS: 12.9 mo | 14 d (7 d-138 d) | overall: 56.8% (25/44);CD19+: 47.7% (21/44);CD19-: 9.1% (4/44) | N/A | 26% (14/53) with sCRS |
Tu S et al. [25] | FMC63-28ζ | lentivirus | N=25, adults, 36 y (18-67 y) | FC | median dose of 7.133×105/kg | CR: 88% (22/25),N/A,median DFS: 257 d,median OS: 267 d | up to 11 mo in one patient | overall: 31.8% (7/22);CD19+: 22.7% (5/22);CD19-: 9.1% (2/22) | N/A | no sCRS |
Maude SL et al. [11] | FMC63-BBζ | lentivirus | N=30, peds (n=25),11 y (5-22 y); adults (n=5),47 y (26-60 y) | none/FC/Cy/CAVD/clofarabine/Cy+VP | (0.76-20.6)×106/kg | CR: 90% (27/30), 6 w-8.5 mo, up to 24 mo,6-month EFS: 67% | at 6 months, the probability of CAR T cell persistence was 68% | overall: 29.2% (7/27);CD19+: 14.8% (4/27), with early loss of CAR T cells;CD19-: 11.1% (3/27) | 2-3 mo | 27% (8/30) with sCRS |
Hu, Y et al. [26] | FMC63-BBζ | lentivirus | N=15, adults<60 y | FC | (1.1-9.8) × 106/kg,dose-escalation | CR: 80% (12/15),1 mo,median LFS: 143 d | up to 7 mo | overall: 50% (6/12);CD19+: 16.7% (2/12);both CD19- and CD19+: 16.7% (2/12);CNS relapse: 16.7% (2/12) | N/A | 40% (6/15) with Gr3 CRS |
Gardner RA et al. [7] | FMC63-BBζ | lentivirus | N=43, peds and young adults, 12.3 y (1.3-25.4 y),4 of whom were <3 y | 14 given FC | 1×106/kg,CD4+:CD8+=1:1 | CR: 93% (40/43), 12.2 mo (1.9-21.5 mo),CR=100% (14/14) in patients after FC,N/A | N/A | overall: 45% (18/40);CD19+: 27.5% (11/40);CD19-: 17.5% (7/40) | median: 3 mo,time from loss of BCA to relapse: 3.7 mo (0-11 mo) | 23% (10/40) with sCRS |
Maude SL et al. [6] | FMC63-BBζ | lentivirus | N=75, peds and young adults | 72 given FC, 1 given EA | (0.2-4.5)×106/kg | CR: 83% (61/75), 3 mo,EFS and OS rates were 73% and 90% at 6 mo and 50% and 76% at 12 mo, respectively | 168 d (20-617 d),as long as 20 mo | overall: 36.1% (22/61);CD19+: 1.6% (1/61);CD19-: 24.6% (15/61) (3 with concomitant CD19+ blasts);unknown: 9.8% (6/61) | probability of BCA at 6 mo after infusion was 83% | 73% (55/75) with Gr 3/4 CRS |
Jiang H et al. [27] | FMC63-BBζ | lentivirus | N=53, peds and adultsrange, 10-61 y (children: 7.5%; young adults: 54.7%; adult: 37.7%) | FC | (0.89-4.01)×106/kg,CD4+:CD8+=1:1 | CR:88.7%(47/53), 3.4mo,(1.1-15.6mo),median OS: 16.1 mo | up to 18 mo | overall: 44.7% (21/47);2 patients with CD19+ relapse at 10 mo and 16 mo;unknown: 40.4% (19/47) | N/A | 35.8% (19/53) with Gr 3/4 CRS |
Hay KA et al. [28] | FMC63-BBζ | lentivirus | N=53, adults, 39 y (20-76 y) | FC/Cy | 2×106/kg,CD4+: CD8+ =1:1 | CR: 85% (45/53), 3.5mo(1.1-17mo),median EFS: 7.6 mo | N/A | overall: 48.9% (22/45); CD19+: 31.1% (14/45), 5 with diminished expression;CD19-: 13.3% (6/45);unknown: 4.5% (2/45) | CD19- relapse group: ongoing;CD19+relapse: 89 d (28-184d) | 19% (10/53) with CRS ≥Gr 3 |
Cheng Z et al. [29] | FMC63-BBζ and FMC63-28ζ | gammaretrovirus | N=6, peds and adults, 26 y (7-45 y) | FC | 1 × 106/kg (mixture of 28ζ CAR T cells and BBζ CAR T cells at a 1:1 ratio) | CR: 57.1% (4/7), 9 mo, (2 mo-18 mo),median OS: 12 mo | N/A | overall: 75% (3/4);CD19+: 50% (2/4);CD19- : 25% (1/4) | N/A | 66.7% (4/6) with Gr 3/4 CRS |
Li S et al. [20] | FMC63-BBζ and FMC63-28ζ | lentivirus | N=10, adults, 5 for CD19-28ζ T cells, 5 for CD19-BBζ T cells, 33 y (18-59 y) | FC | (0.1-9.79)×106/kg | CD28 group:CR: 60% (3/5), 4, 6, 8 mo;4-1BB group:CR: 60% (3/5),2 and 8 mo, and 1 is still alive | no more than 1 mo in most patients;persistence over 2 mo was observed only for a patient in the 4-1BB group | CD28 group: 3/3 CD19+ relapse;4-1BB group: 2/3 CD19+ relapse | 2–4 mo in 6 responders | no adverse events were over Gr 2 |
Cao J et al. [30] | humanized scFv-BBζ | lentivirus | N=18, peds and adults (with or without prior mCAR T cell therapy), 14 y (3-57 y) | FC | 1 × 106/kg | CR: 77.8% (14/18), 125 d (100-205 d), OS and LFS rates at d 180 were 65.8% and 71.4%, respectively | median: 60 d, up to 1 y | overall: 28.6% (4/14); CD19+: 21.4% (3/14);both CD19+ and CD19-: 7.2% (1/14) | median 111 d | 22.2% (4/18) with CRS≥Gr 3 |
Zhao Y et al. [31] | humanized scFv-BBζ | lentivirus | N=5, peds and young adults (with prior mCAR T cell therapy), 14 y (9-21 y) | FC | (0.3-3) × 106/kg | CR: 80% (4/5),N/A | 30 d-11 mo | N/A | 20 d-2 mo | none with CRS>Gr2 |