Table 2.
Summary of efficacy and safety of most relevant B-cell maturation antigen (BCMA)-directed CAR T-cell trials in relapse and refractory multiple myeloma (RRMM).
| Idecabtagene Vicleucel (Ide-Cel) KARMMA Study [23] |
bb21217 [24] | Orvacabtagene-Autoleucel (Orva-Cel) EVOLVE Ph 1/2 Trial [25] |
Ciltacabtagene Autoleucel (Cilta-Cel) CARTITUDE 1 [26] |
LCAR-B38M LEGEND-2 [27] |
|
|---|---|---|---|---|---|
| CAR Design | Autologous, lentiviral vector 4-1BB | Ide-cel cultured with PI3Ki, to enrich memory-like T cells | Fully human (CD28/41BB). 1:1 CD4:CD8 ratio |
2 BCMA-targeting single chain antibody | 2 BCMA-targeting single chain antibody (same as JNJ 4528) |
| Population | 128 (Ph 2) | 38 (Ph 1) | 62 (Ph 1/2) | 29 (Ph 1b/2) | 57 (Ph 2) |
| Number of Prior lines | 6 | 6 | 6 | 5 | 2 |
| CAR T-cell Dose | 150–450 × 106 CAR T-cell | 150–450 × 106 CAR T-cell | 300–600 × 106 CAR T-cell | 0.73 × 106
CAR T-cells/kg |
0.5 × 106
CAR T + Cells/kg |
| Refractory to CD38 MoAb | 94% | 76% | NA | 93% | 1 patients |
| Triple-class Refractory | 84% | 63% | 94% | 86% | -- |
| Extramedullar disease | 39% | NA | 23% | 10% | NA |
| ORR (CR) | 82%* (39%) | NA (33%) | 92% #. (29%) | 100% (86%) | 88% (74%) |
| DOR/PFS/ OS months |
11.3 */12.1 */19.4 | 11.1 &/NA/NA | NA/NA/ NA |
NA/86%@9m/NA | 19.9m In CR: mPFS 28.2 m |
| CRS (G 3/4) | 96% * (6%) | 66% (6%) | 88% # (4%) | 93% (7%) | 90% (7%) |
| Neurotox(G3) | 20% * (6%) | 24% (8%) | 13% # (0%) | 10% (3%) | 2% |
| Reference | (1) Munshi NC, et al. Initial KarMMa results. J Clin Oncol. 2020;38 (suppl; abstr 8503). | (2) Berdeja JG, et al. Blood (Internet). 2019 Nov 13;134 (Supplement_1):927. | (3) Mailankody S, et al. J Clin Oncol. 2020;30 (suppl; abstr 8504). | (4) Usmani SZ, et al. EHA Library. 2020. p. EP926. | (5) Chen L, et al. Blood (Internet) 2019 Nov 13;134 (Supplement_1):1858. |
* Responses at 450 × 106 CAR T dose levels. # Responses at 600 × 106 CAR T dose level. & Responses at 150 × 106 CAR T dose level. ORR: overall response rate. CR: complete response. DOR: duration of response. PFS: progression-free survival. OS: overall survival. CRS: cytokine release syndrome. G 3/4: Grade 3 or 4. Neurotox: neurotoxicity. G3: Grade 3.