Table 1.
Results from selected studies of CAR T-cell therapy in MM
| Site/developer | Target | Vector | Costimulatory molecule | scFv source | N | Median prior lines, n | CRS all grades/grade 3 or 4 (%) | Neurotoxicity all grades/grade 3 or 4 (%) | Response | MRD negative, % (sensitivity) | PFS | Comments |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Data from published articles | ||||||||||||
| National Cancer Institute23 | BCMA | Retrovirus | CD28 | Murine | 24, 16 highest dose | 9.5 (highest dose) | Highest dose: 94/38 | Highest dose: NA/19 | Highest dose: ORR, 81%; CR, 13%. | Highest dose: 69% (7 × 10−4) | Highest dose: 7.1 mo | BCMA expression required. Postinfusion increase in proportion of CD8+ cells noted. |
| Nanjing Legend LCAR-B38M (China)26 | BCMA | Lentivirus | 4-1BB | Non-scFv | 57 of 74 in trial | 3 | 90/7 | 2/0 | ORR, 88%; CR: 68%. | 63% (1 × 10-4) | 15 mo | Targets 2 BCMA epitopes; CAR T cells infused in 3 split doses. |
| Nanjing Legend LCAR-B38M (China)25 | BCMA | Lentivirus | 4-1BB | Non-scFv | 17 of 74 in trial | ≥3: 71% | 100/41 | NA | ORR, 88%; CR, 76%. | NA | 52.9% at 12 mo | No difference in toxicity/persistence of cells based on 3 vs 1 infusion. TLS seen in 3 patients. |
| University of Pennsylvania/Novartis CAR T BCMA24 | BCMA | Lentivirus | 4-1BB | Human | 25, 11 in cohort 3 | 7 | 88/32 | 32/12 | ORR, 48%; CR, 8%. Cohort 3: ORR, 64%; CR: 9%. |
16%; cohort 3: 9% (1 × 10−5) | Cohort 1: 2.1 mo; cohort 2: 1.9 mo; cohort 3: 4.1 mo. | BCMA intensity did not predict response. Responses correlated with CAR T-cell expansion, which was more likely with higher proportion of naive/memory phenotype cells. BCMA declined with treatment, more so in responders. |
| Bluebird/Celgene28 | BCMA | Lentivirus | 4-1BB | Murine | 33 | 7-8 | 76/6 | 42/3 | ORR, 85%; CR, 45%. | 94% (15/16 evaluable) (1 × 10−5 or deeper) | 11.8 mo | Peak expansion correlated with response. |
| University of Pennsylvania/Novartis9 | CD19 | Lentivirus | 4-1BB | Murine | 10 | 6 | 10/0 | 0 | ORR, 80% with Mel, ASCT, and CAR T cells; 20% benefit rate from CAR T cells. | NA | 6 mo | |
| Baylor10 | κ Light chain | Retrovirus | CD28 | Murine | 7 | NA | 0 | 0 | 0% | — | NA | |
| Dana-Farber Cancer Institute20 | NKG2D | Retrovirus | None | Human | 5 | All ≥ 5 | 0 | 0 | 0% | — | NA | |
| Data from published abstracts | ||||||||||||
| JCARH125 Juno/Celgene30 | BCMA | Lentivirus | 4-1BB | Human | 44 | 7 | 80/9 | 25/7 | ORR, 82%; CR, 27%. | NA | NA | 1:1 CD4/CD8 ratio preselected prior to transduction and expansion. Response did not correlate with baseline serum BCMA level. Serum BCMA declined with treatment, more so in responders. |
| MCARH17131 | BCMA | Retrovirus | 4-1BB | Human | 11 | 6 | 55/18 | 9/0 | ORR, 64%; CR, 0%. | NA | NA | No predefined CD4/CD8 ratio. Higher doses correlated with peak expansion. Peak expansion correlated with durability of response. Includes a truncated EGFR safety system. |
| FCARH14336 | BCMA | Lentivirus | 4-1BB | Human | 11 | 11 | 91/0 | 9/NA | ORR, 100%; CR, 36%. | NA | NA | 1:1 CD4/CD8 ratio after transduction and expansion. Encodes surface marker to analyze persistence. BCMA expression required. Includes a truncated EGFR safety system. BCMA antigen loss seen in 1 patient at time of relapse. |
| P-BCMA - 101/Poseida35 | BCMA | Nonviral (PiggyBac) | 4-1BB | Human | 23 | 6 | 9.5/0 | 4.8/4.8 | ORR, 43-100% at various doses. | NA | NA | Nonviral PiggyBac DNA-delivery system: increases memory stem cells to increase persistence. It has a large cargo capacity, drug-resistance gene for positive selection, proprietary safety switch. Peak expansion was delayed/slower (14-21 d); lower CRS. |
| BB21217 Bluebird/Celgene29 | BCMA | Lentivirus | 4-1BB | Murine | 12 | 7 | 67/8 | 25/8 | ORR, 83%; CR, 25%. | 66% (4/6 evaluable) (NA) | NA | Same construct as bb2121. CAR T cells cocultured with PI3K inhibitor (bb007) to enrich for cells with memory phenotype to increase long-term CAR T-cell persistence. |
| HRAIN Biotechnology (China)32 | BCMA | Retrovirus | 4-1BB | NA | 20 | 5.5 | 45/5 | NA | ORR, 85%; CR, 45%. | NA | 15 mo | tEGFR safety switch, BCMA expression required. |
| Tongji Hospital, Huazhong University (China)33 | BCMA | NA | CD28, 4-1BB | Murine | 30 | 4.5 | 97/20 | 3.3 | ORR, 93%; CR, 50%. | NA | 9.9 mo (no EMD or PCL), 4.6 mo (with EMD or PCL). | |
| CT053, Wenzhou University, Carsgen (China)34 | BCMA | NA | 4-1BB | Human | 17 | 4 | 29/6 | NA | ORR, 100%; CR, 36%. | NA | NA | |
| SZ CART MM-02, Jiangsu Institute (China)37 | CD19 and BCMA | Lentivirus | 4-1BB (CD19) and CD28, OX40 (BCMA). | Murine (CD19) and human (BCMA) | 10 | — | 100/0 | 0 | ORR, 100%; CR, 70%. | 60% (1 × 10−6) | NA | Tandem ASCT and separate infusions of CAR T cells targeted against CD19 and BCMA in high-risk MM. Lenalidomide maintenance post CAR T-cell therapy. |
Data are current as of 2 May 2019.
CR, complete response; CRS, cytokine release syndrome; EMD, extramedullary disease; Mel, melphalan; MRD, minimal residual diseases; NA, not available; ORR, overall response rate; PCL, plasma cell leukemia; PI3K, phosphoinositide 3 kinase; PFS, progression-free survival; tEGFR, truncated epidermal growth factor; TLS, tumor lysis syndrome.