Adoptive immunotherapy for acute leukemia: New insights in chimeric antigen receptors

Table 2 Completed chimeric antigen receptor T cells trials including acute leukemia patients

Indications	CAR construct	Vector	Cell dose	Pre-treatment	Patients	Responses	Relapses	CAR persistence (days median)	Toxicities	Ref.
Acute lymphoid malignancies
Relapsed B-ALL ± post-ASCT	Anti-CD19 scFv 4-1BB-CD3ζ	Lentiviral	106-107 cells/kg	Cy	30	90% CR (27/30)	6 relapses (one CD19-)	145	CRS for all responding patients (fever, ARDS. MODS)	[17,97,98]
Relapsed B-ALL post-ASCT	Anti-CD19 scFv CD28-CD3ζ	γ-retroviral	106 cells/kg	Cy + flu	2	100% CR (5/5)	1 transient CR	ND	Mild CRS, no GVHD	[117]
B-ALL relapsed	Anti-CD19 scFv CD28-CD3ζ	γ-retroviral	3 × 106 cells/kg	Chemo	13 (3 Ph+ B-ALL)	85% CR (10/13)	1 NR, 1 relapse	ND	6/13 CRS	[62,94]
B-ALL relapsed without prior ASCT	Anti-CD19 scFv CD28-CD3ζ	γ-retroviral	1.5-3 × 106 cells/kg	Cy	5	100% CR (5/5)	1 relapse (no ASCT)	ND	3/5 mild CRS (MRD+ or bulk)	[63]
Relapsed B-ALL/ CLL post-ASCT	Anti-CD19 scFv CD28-CD3ζ VST (CMV, EBV, ADV)	γ-retroviral	1.5 × 107-1.2 × 108 cells/m2	No	4 (4/8)	75% CR (3/4), 25% PD (1/4)	1 relapse (no ASCT)	80	No CRS, No GVHD	[95]
Acute myeloid malignancies
Relapsed AML	Anti-LeY scFv CD28-CD3ζ	γ-retroviral	1.3 × 109 cells	Chemo	4	25% CR, 50% SD	4 relapses	14-120	Neutropenia, skin “flare” reaction, fever, rigors	[87]

CAR: Chimeric antigen receptor; ADV: Adenovirus; AML: Acute myeloid leukemia; ARDS: Acute respiratory distress syndrom; ASCT: Allogeneic stem cell transplantation; B-ALL: B-lineage acute lymphoblastic leukemia; Chemo: Chemotherapy prior CAR T cells infusion; CLL: Chronic lymphoid leukemia; CMV: Cytomegalovirus; CR: Complete remission; CRS: Cytokine release syndrome; Cy: Cyclophosphamide; EBV: Epstein Barr virus; GVHD: Graft versus host disease; MODS: Multi-organ dysfunction syndrome; ND: Not determined; NR: No response; PD: Progressive disease; SD: Stable disease; VST: Virus specific T lymphocytes.