From: State-of-the-art for CAR T-cell therapy for chronic lymphocytic leukemia in 2019
Clinical context | CAR T characteristics | Efficacy | Toxicity | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Reference/year | Number of CLL patients | Clinical situation | Prior ttmt with ibrutinib | Prior ttmt with venetoclax | TP53 alterations | Complex karyotype | Targeted Ag | Co-stimulation | Cell source | Lymphodepletion | Treatment combination | Responses | CRS all grades N (%) | CRES all grades N (%) | Toxcity-related mortality |
[8] / 2011 | 1 | R/R | 0 | 0 | 1/1 | 0 | CD19 | 4-1BB | Autologous | P + C | None | CR | 1 (100) | 0 | 0 |
[9] / 2011 | 8 | R/R | 0 | 0 | 2/8 | 1/8 | CD19 | CD28 | Autologous | None or C | None | 3/8 SD | 8 (100) | 0 | 1(13) |
[10] / 2011 | 3 | R/R | 0 | 0 | 2/3 | 0 | CD19 | 4-1BB | Autologous | B + R or P + C | None | 3/3 ORR 2/3 CR | 3 (100) | 0 | 0 |
[11] / 2012 | 4 | R/R | 0 | 0 | ND | ND | CD19 | CD28 | Autologous | F + C | IL2 IV for 5 d | 3/4 ORR 1 CR | 4 (100) | 0 | 0 |
[12] / 2013 | 4 2 Richter | Recurrence after allogeneic treatment | 0 | 0 | 2/4 | ND | CD19 | CD28 | Allogeneic | None | None | 1/4 ORR 1 PR 1 SD | ND | ND | 0 |
[13] / 2015 | 5 1 Richter | R/R | ND | ND | ND | ND | CD19 | CD28 | Autologous | F + C | None | 5/5 ORR 3 CR 2 PR | 3 (60) | 1 (20) | 0 |
[14] / 2015 | 14 | R/R | 1/14 | 0 | 6/14 | ND | CD19 | 4-1BB | Autologous | B or P+ C or F + C | None | 8/14 ORR (57%) 4/14 CR (28%) 4/14 PR (28%) 4 MRD neg | 9 (64) | 5 (36) | 0 |
[15] / 2016 | 3 | R/R | 3/3 | 0 | 3/3 | 2/3 | CD19 | 4-1BB | Autologous | ND | Ibrutinib stopped just before leukapheresis | 3/3 ORR 1 CR 2 PR | ND | ND | ND |
[16] / 2016 | 5 | Recurrence after allogeneic treatment | ND | ND | ND | ND | CD19 | CD28 | Allogeneic | None | None | 2/5 ORR 1 CR 1 PR | 4 (80) | 0 | 0 |
[17] / 2016 | 2 | R/R | 0 | 0 | ND | ND | Kappa | CD28 | Autologous | None | None | 0 ORR 1 SD | ND | ND | ND |
[18] / 2017 | 24 5 Richter | R/R post-ibrutinib 25% post venetoclax | 24/24 | 6/24 | 23/24 | 16/24 | CD19 | 4-1BB | Autologous | F + C mostly, or F or C | None | 71% ORR 21% CR 43% PR 58% MRD neg | 20 (83) | 8 (33) | 1 (4) |
[19] / 2018 | 8 | 1st line P + FC | 0 | 0 | 0 | 0 | CD19 | CD28 | Autologous | C | None | 3/8 ORR (38%) 2/8 CR | 4 (50) | 0 | 0 |
[20] / 2018 | 19 4 Richter | R/R post-ibrutinib | 19/19 | 11/19 | 14/19 | 14/19 | CD19 | 4-1BB | Autologous | F + C | Concomitant ibrutinib | 15/18 ORR (83%) 11/13 CR BM with MRD neg | 14 (74) | 6 (32) | 1 (5) |
[21] / 2018 | 19 | R/R ×14 +1st line ibrutinib ×5 | 5 in 1st line | 0 | 11/19 | ND | CD19 | 4-1BB | Autologous | ND“chemotherapy” | Concomitant ibrutinib | 10/11 ORR 94 CR BM with 78% MRD neg | 18 (95) | 5 (26) | 0 |
[22] / 2018 | 16 | R/R post-ibrutinib | 16/16 | 8/16 | 10/16 | 8/16 | CD19 | 4-1BB | Autologous | F + C | None | 81.3% ORR 7 CR 6 PR | 12 (75) | 1 (6) | 0 |