Maude SL5050 Maude SL. Efficacy of humanized CD19-targeted chimeric antigen receptor (CAR)-modified T cells in children with relapsed ALL. Maude SL, Barret DM, Rheingold SR, Aplenc R, Teachy DT eat al. ASCO 2016 abstract 3007. ASCO 2016 Philadelphia UPenn |
Pediatric |
FMC63-4-1BB-z |
59 |
Cy 43% Flu Cy |
55/59 (93%) 88% |
12 months SLD - 55% SG - 79% |
36% (20/55) |
24% (13/55) |
|
|
Maude SL1010 Maude SL, Laetsch TW, Buechner J, Rives S, Boyer M, Bitten- court H, et al. Tisagenlecleucel in children and young adults with B-Cell lymphoblastic leukemia. N Engl J Med. 2018;378 (5):439-48. NEJM 2018 ELIANA trial Fase II |
Pediatric AYA |
FMC63-4-1BB-z |
92 (75) |
Flu Cy |
61/75 (81%) 81% |
12 months SLD - 50% SG - 76% |
33% (20/61) |
25% (15/61) |
8/75 |
61% previous HSCT |
Lee DW5151 Lee DW, Kochendorfer JN, Settler-Stevenson M, Cui YK, Del- brook C, Feldman SA, et al. T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in chil- dren and young adults: a phase 1 dose-escalation trial. Lancet. 2015 Feb 7;385(9967):517-28. Lancet 2015/ Blood 20165252 Lee DW. Long-term outcomes following CD19 CAR T cell ther- apy for B-ALL are superior in patients receiving a fludarabine/ cyclophosphamide preparative regimen and post-CAR hematopoietic stem cell transplantation. Blood. 2016;128 (22):218. Abstract ASH 2016. NCI Phase II |
Pediatric AYA |
FMC63-CD28-z |
51 |
Flu Cy |
31/51 (60,8%) 28/31 (90%) |
18 months SLD - 49,5% |
29% (8/28) |
18% (5/25) |
21/28 |
Significant improvement in survival with HSCT (= 0.0006) |
Gardner RA2929 Gardner RA, Finney O, Annesley C, Brakke H, Summers C, Leger K, et al. Intent-to-treat leukemia remission by CD19 CAR T cells of defined formulation and dose in children and young adults. Blood. 2017;129(25):3322-31., Blood 2017 Seattle Fase I |
Pediatric AYA |
FMC63-4-1BB-z |
45 |
Flu Cy |
40/45 89% |
12 months SLE - 50.8% SG - 69.5% |
45% (18/40) |
18% (7/40) |
11/40 |
62% previous HSCT |
Pasquini MC1414 Pasquini MC, Hu ZH, Curran K, Laetsch T, Locke F, Rouce R, et al. Real-world evidence of tisagenlecleucel for pediatric acute lymphoblastic leukemia and non-Hodgkin lymphoma. Blood Adv. 2020;4(21):5414-24., Blood Adv 2020
|
Pediatric AYA |
FMC63-4-1BB-z |
255 |
Flu Cy |
85,5% 115/116 |
12 months SLE - 52.4% SG - 77.2% |
- |
NA |
34/218 |
27.8% previous HSCT |
Hay KA4646 Hay KA, Gauthier J, Hirayama AV, Voutsinas JM, Wu Q, Li D, et al. Factors associated with durable EFS in adult B-cell ALL patients achieving MRD-negative CR after CD19 CAR T-cell therapy. Blood. 2019 Apr 11;133(15):1652-63. https://doi.org/10.1182/blood-2018-11-883710 https://doi.org/10.1182/blood-2018-11-88...
, Blood 2019 Fred Hutchinson Fase I |
Adult |
FMC63-4-1bb-z |
53 |
79% Flu Cy |
45/53 (85%) 100% |
SG - 20 months SLE -7.6 months |
31% (9/29)* |
7% (2/29)* |
18/45 |
43 % previous HSCT |
Park JH2727 Park JH, Riviere I, Gonen M, Wang X, Sénéchal B, Curran KJ, et al. Long-term follow-up of CD19 CAR therapy in acute lym- phoblastic leukemia. N Engl J Med. 2018;378(5):449-59., NEJM 2018 Memorial Sloan-Kettering Fase I |
Adult
|
SJ25C1-CD28-z |
53 |
Flu Cy |
44/53 (83%) 32/48 (67%) |
SG-12.9 months SLE-6.1 months |
57% (25/44) |
9% (4/44) |
17/44 |
36% previous HSCT |
Pan J et al5353 Pan J, Yang JF, Deng BP, Zhao XJ, Zhang X, Lin YH, et al. High efficacy and safety of low-dose CD19-directed CAR-T cell ther- apy in 51 refractory or relapsed B acute lymphoblastic leuke- mia patients. Leukemia. 2017 Dec;31(12):2587-93., Leukemia 2017 |
Adult and pediatric |
4-1BB-z |
42 9 |
Flucy |
36/40 (90%) 34/40 (85%) |
|
11/45 2 after HSCT |
NA |
27/45 |
|
Frey NV5454 Frey NV, Shaw PA, Hexner EO, Pequignot E, Gill S, Luger SM, et al. Optimizing chimeric antigen receptor T-Cell therapy for adults with acute lymphoblastic leukemia. J Clin Oncol. 2020 Feb 10;38(5):415-22., JCO 2020 UPenn |
Adult |
FMC63-4-1BB-z |
35 |
25 somente Cy
|
24/35 (69%) 19 DRM - |
SG - 19,5 months SLE - 5.6 months |
|
NA |
9/24 |
37% previous HSCT |
Gu R et al5555 Gu R, Liu F, Zou D. Efficacy and safety of CD19 CAR T con- structed with a new anti-CD19 chimeric antigen receptor in relapsed or refractory acute lymphoblastic leukemia. J Hematol Oncol. 2020;122. https://doi.org/10.1186/s13045-020-00953-8 https://doi.org/10.1186/s13045-020-00953...
, BMC 2020 |
Pediatric and adult |
HI19α-4-1BB-ζ |
22 |
Flu Cy |
82% 18/18 100% |
SLD - 6.9 months SG - 12.9 months |
8/18 |
3/8 |
|
|
Zhang X et al.5656 Zhang X, Lu X-a, Yang J, Zhang G, Li J, Song L, et al. Efficacy and safety of anti-CD19 CAR T-cell therapy in 110 patients with B- cell acute lymphoblastic leukemia with high-risk features. Blood Advances. 2020 May 26;4(10):2325-38. https://doi.org/10.1182/bloodadvances.2020001466.2020 . https://doi.org/10.1182/bloodadvances.20...
, Blood Adv 2020 |
Pediatric and adult |
89 - 4-1BB-z 21 - CD28-z |
110 |
Flu Cy |
92.7% 87.3% |
SG: (HSCT vs. not) 79.1% vs. 32.0% SLD: (HSCT vs. not) 76.9% vs. 11.6%; |
23/110 |
7/23 |
75/102 |
16/110 previous HSCT Significant improvement in survival with allogeneic HSCT |
Shah BD1717 Shah BD, Ghobadi A, Oluwole OO, Logan AC, Boissel N, Cassa- day RD, et al. KTE-X19 for relapsed or refractory adult B-cell acute lymphoblastic leukaemia: phase 2 results of the single- arm, open-label, multicentre ZUMA-3 study.Lancet. 2021;398 (10299):491-502., Lancet 2021 ZUMA-3 |
Adult |
|
55 |
Flu Cy |
39 (71%) 38/39 (99%) |
12 months SG - 71% 6 months SLD - 58% |
12/39 |
|
12/39 |
42% previous HSCT |
Shah N5757 Shah NN, Lee DW, Yates B, Yuan CM, Shalabi H, Martin S, et al. Long-term follow-Up of CD19-CAR T-cell therapy in children and young adults with B-ALL. J Clin Oncol. 2021 May 20;39 (15):1650-9. https://doi.org/10.1200/JCO.20.02262 Epub 2021 Mar 25. PMID: 33764809; PMCID: PMC8274806. https://doi.org/10.1200/JCO.20.02262...
, JCO 2021 Fase I |
Pediatric and Adult |
28ζ |
50 |
Flu-Cy and others |
62% 90.3% |
4.8 years SG - 10.5 months |
9.5% after HSCT |
|
75% |
SLE 5 years after HSCT - 62% |