Table 1 CAR T cells in multiple myeloma early-phase clinical trials
From: Cell-based immunotherapy approaches for multiple myeloma
Antigen/ Reference | Trial design | CAR construct/ vector | CAR T cell dose | Conditioning/ lymphodepletion | Patients reported | Safety/side effects | Anti-tumour activity |
|---|---|---|---|---|---|---|---|
BCMA | |||||||
Ali et al.,22 Brudno et al.23 National Cancer Institute, National Institutes of Health, Bethesda | Phase I dose-escalation study | Costimulation: CD28 Vector: γ retroviral | 0.3–9 × 106 cells/kg body weight | Cyclophosphamide (3 × 300 mg/m2) and fludarabine (3 × 30 mg/m2) | r/r MM, n = 27 | CRS and prolonged cytopenias in patients treated on the 9 × 106 cells/kg dose level | Anti-tumour activity of BCMA-CAR T cells in poor-prognosis MM demonstrated |
University of Pennsylvania, Philadelphia | Phase I dose-escalation study | Costimulation: 4-1BB Vector: lentiviral | DL 1: 1–5 × 108 cells DL 2: 1–5 × 107 cells DL 3: 1–5 × 108 cells (absolute number) | DL 1: none DL 2/3: cyclophosphamide 1.5 g/m2 | r/r MM, n = 21 | CRS (n = 17), severe reversible neurotoxicity (n = 3) | Promising in vivo CAR T cell expansion and clinical activity, even without lymphodepletion Depth of response correlates with degree of BCMA-CAR T cell expansion and CRS |
Multicentre | Multicentre phase I dose-escalation study | Costimulation: 4-1BB Vector: lentiviral | 50–1200 × 106 cells (absolute number) | Cyclophosphamide (3 × 300 mg/m2) and fludarabine (3 × 30 mg/m2) | r/r MM, n = 21 | CRS (n = 17) | Promising efficacy (100% ORR) at dose levels above 50 × 106 cells |
Smith et al.28 Memorial Sloan-Kettering Cancer Center, New York | Phase I dose-escalation study | Costimulation: 4-1BB Vector: retroviral | DL 1: mean 72 × 106 cells DL 2: mean 137 × 106 cells (absolute number) | DL 1: cyclophosphamide (1 × 3 g/m2) DL 2: cyclophosphamide/ fludarabine (3 × 300/30 mg/m2) | r/r MM, n = 6 | CRS grade 1–2 (n = 3) | Promising anti-tumour activity in highly pretreated patients |
Mi et al.,31 Fan et al.30 Shanghai Institute of Hematology, Shanghai Jiao Tong University, Shanghai | Phase I | Antigen recognition: bi-epitope Costimulation: not published vector: not published (LCAR-B38M) | Median 4.7 × 106 cells/kg BW infused over 3 days | Cyclophosphamide (3 × 250 mg/m2) and fludarabine (3 × 25 mg/m2) | r/r MM, n = 19 | CRS (n = 14) | Objective response achieved in all patients, CR/nCR in 19 patients |
CD19 | |||||||
Garfall et al.33, 34 University of Pennsylvania, Philadelphia | Phase I | Costimulation: 4-1BB Vector: lentiviral (CTL019) | 1–5 × 107 cells (absolute number) | Melphalan (140–200 mg/m2) and ASCT | r/r MM, n = 10 | Most toxicity attributable to ASCT, no severe CRS | CTL019 may prolong response of standard MM therapies |
CD138 | |||||||
Guo et al.38 General Hospital of PLA, Beijing | Phase I | Costimulation: 4-1BB Vector: lentiviral | 0.756 × 107 cells/kg BW | CP or PCD or VAD | r/r MM, n = 5 | No intolerable toxicities, grade 3 fever upon CAR T cell infusion | Feasibility demonstrated, stable disease in four patients longer than 3 months |
κ-light-chain | |||||||
Ramos et al.39 Baylor College of Medicine, Houston | Phase I | Costimulation: CD28 Vector: retroviral | 0.2–2 × 108 cells/m2 BS | Cyclophosphamide (12.5 mg/kg) in patients without lymphopenia | r/r MM, n = 7 | No toxicities attributable to CAR T cells | Stable disease 4 patients lasting 2–17 months |
NKG2D ligands | |||||||
Nikiforow et al.43 Dana-Farber Cancer Institute, Boston | Phase I dose-escalation study | Receptor design: NKG2D, DAP10 signal transmission subunit, CD3ζ Signalling domain vector: retroviral (CM-CS1) | 1 × 106–3 × 107 cells (absolute number) | None | r/r MM, n = 5 | Safety demonstrated, no dose-limiting toxicity | Feasibility demonstrated |
