Table 3 Representative clinical trials and outcomes of CAR-T monotherapy for treating hematologic malignancies

Monospecific, autologous

Tisagenlecleucel, CD19

FMC63 scFv, 4-1BB

ELIANA

I/II

R/R B-ALL

1–8 (median 3)

75

ORR 81%,

CR/CRi 81%

EFS 50%, OS 76% (12months)

Yes

⁴¹⁸

JULIET

II

R/R DLBCL

1–6 (median 3)

93

ORR 52%,

CRR 40%

RFS 65%, OS 49% (12 months)

Yes

⁴¹⁹

BELINDA

III

Aggressive B-NHL

1

322

ORR 46.3%

PFS 25.9% (6 weeks)

Yes

⁴²⁰

ELARA

II

R/R FL

2–13 (median 4)

97

ORR 86.2%,

CRR 69.1%

PFS 67% (12 months)

Yes

⁴²¹

Axicabtagene ciloleucel (KTE- X19), CD19

FMC63 scFv, CD28

ZUMA-1

I/II

R/R LBCL

1–4 (median 3)

101

ORR 82%,

CRR 58%

PFS 44% (12months), OS 52% (18 months)

Yes

⁴²²

Brexucabtagene, CD19

FMC63 scFv, CD28

ZUMA-2

II

R/R MCL

1–5 (median 3)

71

ORR 93%,

CRR 67%

PFS 61%, OS 83% (12months)

Yes

⁴²³

Axicabtagene ciloleucel (KTE- X19), CD19

FMC63 scFv, CD28

ZUMA-3

I/II

R/R B-ALL

≥2 (median 2)

55

CR/CRi: 71%

Median RFS 11.6 months, median OS 18.2 months

–

⁴²⁴

ZUMA-5

I/II

R/R FL or MZL

2–3 (median 3)

153

ORR 96%,

CRR 77%

PFS 74%, OS 93% (12 months)

–

⁴²⁵

ZUMA-7

III

R/R LBCL

1

179

ORR 83%,

CRR 65%

EFS 41% (24 months)

–

⁴²⁶

ZUMA-12

I/II

High-risk LBCL

Untreated

40

ORR 89%,

CRR 78%

PFS 75%, OS 91% (12 months)

Yes

⁴²⁷

PD1-19bbz, CD19

Anti-CD19 scFv, 4-1BB

NCT04213469

I

R/R B-NHL

Not treated with CAR-T

8

ORR 100%,

CRR 87.5%

PFS 100% (12 months)

No

⁴⁶⁵

Lisocabtagene maraleuecel, CD19

FMC63 scFv, 4-1BB

TRANSCEND NHL001

I

R/R LBCL

1–4 (median 3)

269

ORR 73%,

CRR 53%

Median follow-up for OS 18.8 months

Yes

²⁶⁷

TRANSFORM

III

R/R LBCL

1

92

ORR 79%,

CRR 61%

PFS 52.3%, OS 79.1% (12 months)

Yes

⁴²⁹

PILOT

II

R/R LBCL

1 (without HSCT)

61

ORR 49%,

CRR 33%

Median PFS 9.03 months

Yes

⁴³⁰

TRANSCEND CLL 004

I

R/R CLL/SLL

≥2 (median 4)

23

ORR 82%,

CRR 45%

Median PFS 18 months

Yes

⁴²⁸

CD20 CAR-T

/

ChiCTR2000036350

I

R/R B-NHL

1

15

ORR 100%,

CRR 80%

PFS and OS 100% (12.4 months)

No

⁴³¹

CD22 CAR-T

Anti-CD22 scFv, 4-1BB

NCT02315612

I

R/R B-ALL

≥1 (except 1 untreated)

21

CRR 57%

Among the 12 patients who attained CR, 3 remain in ongoing CR at 21, 9 and 6 months. 8 patients relapsed 1.5–12 months post CAR infusion.

No

⁴³²

Monospecific, universal (allogenic)

ALLO-501A, CD19

Anti-CD19 scFv, with disrupted TCRα and edited CD52 gene

ALPHA2

I/II

R/R LBCL

≥2

15

ORR and CR 50%

/

No

⁴⁵⁶

CTX110, CD19

Anti-CD19 scFv, with disrupted TCR and elimination of β₂-microglobulin gene

CARBON

I

R/R LBCL

≥2

32

ORR 67%, CRR 41%

Nearly 50% patients received CR maintained it out to at least 6 months

No

⁴⁵⁹

PBCAR0191, CD19

Anti-CD19 scFv, with TCR/CD3 knockout

NCT03666000

I/II

R/R B-ALL

≥2

15

CR/CRi 60%

One patient achieved progression-free more than 250 days. Others had progression or died less than 150 days.

No

⁴⁶¹

R/R B-NHL

≥2

13

ORR 77%, CRR 54%

Duration of response assessment is ongoing.

No

⁴⁶⁰

UCART22, CD22

anti-CD22 scFv,4-1BB

BALLI-01

I

R/R B-ALL

≥1

9

CRi 11%

/

No

⁴⁵⁷

Bispecific, autologous

CD19/22-CAR T

Anti-CD19 FMC63 scFv and anti-CD22 m971 scFv, 4-1BB

NCT03233854

I

R/R B-ALL/ LBCL

≥2

38

B-ALL: ORR 100%, CRR 88%;

LBCL: ORR 62%, CRR 29%

B-ALL: median OS 11.8 months, median PFS 5.8 months

LBCL: median OS 22.5 months, median PFS 3.2 months

No

⁴³³

LV20.19, CD19/20

Anti-CD19 FMC63 scFv and anti-CD20 leu-16 scFv, 4-1BB

NCT03019055

I

R/R B-NHL, CLL

2–12 (median 4)

22

ORR 82%, CRR 64%

Median OS 20.3 months

No

⁴³⁴

TanCAR7 T cells, CD19/CD20

Anti-CD19 FMC63 scFv and anti-CD20 leu-16 scFv, 4-1BB

NCT03097770

I/II

R/R B-NHL

≥1 (most are 3–5)

28

ORR 79%, CRR 71%

PFS 64% (12 months)

No

³⁰²

Bispecific, universal (allogenic)

CTA101, CD19/CD22

Anti-CD19 FMC63 and anti-CD22 m971 scFv with CRISPR/Cas9-disrupted TCRα region and CD52 gene, 4-1BB

NCT04227015

I

R/R B-ALL

≥1

6

CR/CRi 83.3%

50% patients remained MRD negative at a median follow-up of 4.3 months

No

³⁰¹

Monospecific, autologous

CD30.CAR-Ts, CD30

Anti-CD30 scFv derived from HSR3 antibody, 4-1BB

NCT02690545

NCT02917083

II

R/R HL

2–23 (median 7)

41

ORR 62%, CRR 51%

PFS 36%, OS 94% (1 year)

No

⁴³⁵

CD30.CAR-Ts, CD30

NCT01316146

I

R/R HL/ALCL

≥3

9

ORR 33.3%

HL; 1 patient remained CR for 2.5 years, 1 patient remained CR for 2 years

ALCL: 1 patient remained CR for 9 months

No

⁴³⁶

CART-30, CD30

NCT02259556

I

R/R HL

≥10

18

ORR 39%

Median PFS 6 months

No

⁴³⁷

Monospecific, autologous

Idecabtagene vicleucel (ide-cel, bb2121), BCMA

Murine anti-BCMA scFv, 4-1BB

NCT02658929

I

R/R MM

3–23 (median 7)

33

ORR 85%, CRR 45%

Median PFS 11.8 months

Yes

⁴³⁸

KarMMa

II

R/R MM

3–16 (median 6)

128

ORR 73%, CRR 33%

Median PFS 8.8 months

Yes

⁴³⁹

KarMMa

III

R/R MM

2–4

254

ORR 71%, CRR 39%

Median PFS 13.3 months

Yes

⁴⁴⁰

bb21217, BCMA

CRB-402

I

R/R MM

3–17 (median 6)

69

ORR 60%, CRR 28%

Median PFS was not reached

No

⁴⁴¹

Ciltacabtagene autoleucel, BCMA

Llama- derived anti-BCMA VHH, 4-1BB

CARTITUDE-1

I/II

R/R MM

4–8 (median 6)

97

ORR 97%, sCR 67%

PFS 77%, OS 89% (12 months)

Yes

⁴⁴²

CT103A, BCMA

Fully human anti-BCMA scFv, 4-1BB

ChiCTR1800018137

I

R/R MM

3–6 (median 4)

18

ORR 100%, sCR/CR 72.2%

PFS 58.3% (12 months)

No

²⁷⁸

P-BCMA-101, BCMA

Murine anti-BCMA scFv, 4-1BB

PRIME

I/II

R/R MM

2–18 (median 8)

53

ORR 57%

/

No

⁴⁴³

Orva-cel, BCMA

Humanized anti-BCMA scFv, 4-1BB

EVOLVE

I/II

R/R MM

3–18 (median 6)

62

ORR 92%, CRR 36%

/

No

⁴⁴⁴

CT053, BCMA

Humanized anti-BCMA scFv, 4-1BB

Lummicar-2

I/II

R/R MM

2–11 (median 4)

14

ORR 100%, sCR/CR 40%

/

No

⁴⁴⁵

Monospecific, universal (allogenic)

ALLO-715, BCMA

Humanized anti-BCMA scFv with CD52 & TCR knockout, 4-1BB

UNIVERSAL

I

R/R MM

3–11 (median 5)

43

ORR 55.8%

Median DOR 8.3 months

No

⁴⁴⁶

Monospecific, autologous

MCARH109, GPRC5D

Humanized anti-GPRC5D scFv, 4-1BB

NCT04555551

I

R/R MM

4–14 (median 6)

17

ORR 71%, CRR 35%

PFS 50% (10.1 months)

No

²⁹⁹

CC-95266, GPRC5D

Anti-GPRC5D scFv, 4-1BB

NCT04674813

I

R/R MM

≥3

17

ORR 89%, CR 47%

PFS 88% (at the time of analysis)

No

⁴⁴⁸

OriCAR-017, GPRC5D

Anti-GPRC5D scFv with Ori, 4-1BB

POLARIS

I

R/R MM

≥3

10

ORR 100%, sCR 60%

PFS 80% (12months)

No

²⁹⁰

Combination of two monospecific CAR-T

CD19 and BCMA CAR-T

Humanized anti-CD19 scFv, murine anti-BCMA scFv, 4-1BB

ChiCTR-OIC-17011272

II

R/R MM

5–8 (median 6)

21

ORR 95%, sCR 43%, CR 14%

PFS 85% (602 days)

No

⁴⁵⁰

Bispecific, autologous

BM38, BCMA/CD38

Humanized anti-BCMA/CD38 scFv, 4-1BB

ChiCTR1800018143

I

R/R MM

2–9 (median 4)

23

ORR 87%, sCR/CR 54.5%

Median PFS 17.2 months

No

²⁹¹

BCMA/CS1

Murine anti-BCMA/CS1 scFv, 4-1BB

NCT04662099

I

R/R MM

≥2

16

ORR 100%,

sCR 31%

OS 83.9%, PFS 55.2% (12 months)

No

⁴⁴⁹

Monospecific, HSCT donor-derived (allogenic)

CD7 CAR-T

Anti-CD7 scFv, 4-1BB

ChiCTR2000034762

I

R/R T-ALL

2–4 (median 3)

20

ORR 95%, CRR 90%

/

No

²⁸⁴

Monospecific, autologous

nanobody-derived fratricide-resistant CD7-CAR T

Humanized anti-CD7 nano- body-derived CAR, ICOS and 4-1BB

NCT04004637

I

R/R T-ALL/LBL

≥4

8

CRR 87.5%

/

No

²⁸⁵

Monospecific, autologous/donor-derived

NS7CAR, CD7

/

NCT04572308

I

R/R T-ALL/LBL

≥1

20

CRR 95%

/

No

⁴⁵⁴

Monospecific, universal (allogenic)

RD13-01, CD7

Anti-CD7 scFv with TCR/CD3 knockout and NK cell inhibitor, 4-1BB

NCT04538599

I

R/R T-ALL/LBL

2–7 (median 4)

12

ORR 81.8%, CRR 63.6%

/

No

²⁸¹

Monospecific, autologous

CAR-T-38, CD38

Anti-CD38 scFv same as daratumumab, CD28 and 4-1BB

NCT04351022

I

R/R AML

>1 (received HSCT)

6

CR/CRi 66.7%

Median OS 7.9 months, LFS 6.4 months

No

²⁸⁹

NKG2D CAR-T

Humanized NKG2D gene, without co-stimulation domain

NCT02203825

I

R/R AML/MDS/MM

0–4

12

ORR not seen

Median OS 4.7 months

No

⁴⁵¹

CLL-1 CAR-T

Anti-CLL-1 scFv, 4-1BB

ChiCTR2000041054

I

R/R AML

2–10 (median 5)

10

CR/CRi 70%

/

No

⁴⁵²

Monospecific, universal (allogenic)

UCART123v1.2, CD123

Anti-CD123 scFv, with disrupted TRAC and CD52 genes

Ameli-01

I

R/R AML

≥2 or received prior allogenic HSCT

8

ORR 25%

/

No

⁴⁵³