Survival outcomes and efficacy of autologous CD19 chimeric antigen receptor-T cell therapy in the patient with diagnosed hematological malignancies: a systematic review and meta-analysis

Figures & data

Figure 1 Flow diagram of the selection process.

Table 1 Patients Characteristics

Name of author	No. of patients	Category of patients	Type of disease	Method of gene transfer	Ag recognition moieties	Costimulatory domains	Origin of T cells
Turtle 2015^Citation13	34	Adult	B NHL=28	Lentivirus	CD19	4-1BB	Autologous
			CLL=6
Porter 2015^Citation14	14	Adult	CLL	Lentivirus	CD19	4-1BB	Autologous
Porter 2014^Citation15	26	Adult	CLL	Lentivirus	CD19	4-1BB	Autologous
Schuster 2015^Citation16	24	Adult	B-NHL	Lentivirus	CD19	4-1BB	Autologous
Porter 2014^Citation15	12	Adult	ALL	Lentivirus	CD19	4-1BB	Autologous
Grupp 2015^Citation17	53	Pediatric	ALL	Lentivirus	CD19	4-1BB	Autologous
Lee 2015^Citation18	20	Pediatric	ALL	Retrovirus	CD19	CD28	Autologous
Kochendefer 2012^Citation19	8	Adult	B NHL	Retrovirus	CD19	CD28	Autologous
			CLL
Kochenderfer 2015^Citation20	15	Adult	B-NHL	Retrovirus	CD19	CD28	Autologous
Brentjens 2013^Citation21	46	Adult	ALL	Retrovirus	CD19	CD28	Autologous
Turtle 2015^Citation13	29	Adult	ALL	Lentivirus	CD19	4-1BB	Autologous
Savoldo 2011^Citation22	6	Adult	NHL	Retrovirus	CD19	CD28	Autologous
Maude 2014^Citation4	30	Pediatric	ALL	Retrovirus	CD19	4-1BB	Autologous
Kalos 2011^Citation23	3	Adult	ALL	Retrovirus	CD19	CD28	Autologous

Table 2 Response rate subgroup analyses

Name of author	Lymphodepletion Chemotherapy	Culture time of T cells	Generation of CART	Number of infused T cells	Treatment Response
Turtle 2015^Citation13	Cyclophosphamide 60 mg/kg ×1± etoposide OR Cyclophosphamide 60 mg/kg ×1± Fludarabine 25 mg/m^2×3 days	12 days	2^nd	2×10^5, 2×10^6 and 2×10^7/kg	CR=13
					PR=7
Porter 2015^Citation14	NA	10–12 days	2^nd	0.14–11×10^8/kg	CR=4
					PR=4
Porter 2014^Citation15	NA	10–12 days	2^nd	5×10^7 vs 5×10^8	CR=5
					PR=4
Schuster 2015^Citation16	NA	10 days	2^nd	3.08–8.87×10^Citation6/kg	CR=15
Porter 2014^Citation15	NA	10 days	2^nd	6.5–8.45×10^Citation6/kg	CR=8
Grupp 2015^Citation17	NA	13 days	2^nd	1.07–17.36×10^Citation6/kg	CR=50
Lee 2015^Citation18	Cyclophosphamide 900 mg/kg ×1+ Fludarabine 25 mg/m^2×3 days	11 days	2^nd	1×10^6 vs 3×10^6/kg	CR=14
Kochendefer 2012^Citation19	Cyclophosphamide 60 mg/kg ×2+ Fludarabine 25 mg/m^2×5 days	24 days	2^nd	0.3–3.0×10^7/kg	CR=1
					PR=5
Kochenderfer 2015^Citation20	Cyclophosphamide 60 mg/kg ×1–2+ Fludarabine 25 mg/m^2×5 days	11 days	2^nd	1–5×10^6/kg	CR=8
Brentjens 2013^Citation21	Cyclophosphamide 60 mg/kg ×1+ Fludarabine 25 mg/m^2×3 days	8 days	2^nd	1×10^6 vs 3×10^6/kg	CR=37
Turtle 2015^Citation13	Cyclophosphamide 60 mg/kg ×1+ Fludarabine 25 mg/m^2×3 days	14 days	2^nd	2×10^5, 2×10^6 and 2×10^7/kg	CR=24
Savoldo 2011^Citation22	NA	6–18 days	2^nd	1–5×10^6/kg	PD=4
					SD=2
Maude 2014^Citation4	Cyclophosphamide 60 mg/kg ×1+ Fludarabine 25 mg/m^2×3 days OR Cyclophosphamide 60 mg/kg ×1± etoposide	12 days	2^nd	0.3–9.58×10^8/kg	CR=27
					NR=3
Kalos 2011^Citation23	Cyclophosphamide, Pentostain, Bendamustine, Rituximab	10 days	3^rd	0.14–11×10^8/kg	CR=2
					PR=1

Figure 2 Forest plot for response rate and 95% CI based on individual study and the entire study.

Figure 3 Forest plot for CRS toxicity and 95% CI based on individual study and the entire study.

Table 3 Response rate subgroup analyses

Prognostic factor	No. of study	Response rate (95%CI)	P-value
Lymphodepletion Yes No	8 6	0.77 (0.67–0.83) 0.66 (0.41–0.83)	0.001
T cell culture time More than 14 days Less than 14 days	4 10	0.67 (0.56–0.76) 0.65 (0.53–0.76)	0.203
Total CAR-T cells infused More than 10^Citation7 Less than 10^Citation7	6 8	0.80 (0.52–0.99) 0.77 (0.67–0.84)	0.193
Category of patient Adult Paediatric	11 3	0.72 (0.56–0.84) 0.66 (0.52–0.78)	0.054

Figure 4 Progression-free survival (PFS) curve.

Figure 5 Overall survival (OS) curve.

Figure 6 Funnel plot of response rate for publication bias.

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