The present and future of CAR T-cell therapy for adult B-cell ALL Available to Purchase

3.

Kantarjian

H

,

Stein

A

,

Gökbuget

N

, et al.

Blinatumomab versus chemotherapy for advanced acute lymphoblastic leukemia

.

N Engl J Med

.

2017

;

376

(

9

):

836

-

847

.

4.

Kantarjian

HM

,

DeAngelo

DJ

,

Stelljes

M

, et al.

Inotuzumab ozogamicin versus standard therapy for acute lymphoblastic leukemia

.

N Engl J Med

.

2016

;

375

(

8

):

740

-

753

.

5.

Gökbuget

N

,

Dombret

H

,

Bonifacio

M

, et al.

Blinatumomab for minimal residual disease in adults with B-cell precursor acute lymphoblastic leukemia

.

Blood

.

2018

;

131

(

14

):

1522

-

1531

.

6.

Jabbour

E

,

Haddad

FG

,

Short

NJ

,

Kantarjian

H

.

Treatment of adults with Philadelphia chromosome–positive acute lymphoblastic leukemia—from intensive chemotherapy combinations to chemotherapy-free regimens: a review

.

JAMA Oncol

.

2022

;

8

(

9

):

1340

-

1348

.

7.

Maude

SL

,

Frey

N

,

Shaw

PA

, et al.

Chimeric antigen receptor T cells for sustained remissions in leukemia

.

N Engl J Med

.

2014

;

371

(

16

):

1507

-

1517

.

8.

Maude

SL

,

Laetsch

TW

,

Buechner

J

, et al.

Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia

.

N Engl J Med

.

2018

;

378

(

5

):

439

-

448

.

9.

Shah

BD

,

Ghobadi

A

,

Oluwole

OO

, et al.

KTE-X19 for relapsed or refractory adult B-cell acute lymphoblastic leukaemia: phase 2 results of the single-arm, open-label, multicentre ZUMA-3 study

.

Lancet Lond Engl

.

2021

;

398

(

10299

):

491

-

502

.

10.

Frey

NV

,

Gill

S

,

Hexner

EO

, et al.

Long-term outcomes from a randomized dose optimization study of chimeric antigen receptor modified T cells in relapsed chronic lymphocytic leukemia

.

J Clin Oncol

.

2020

;

38

(

25

):

2862

-

2871

.

11.

Roddie

C

,

Dias

J

,

O’Reilly

MA

, et al.

Durable responses and low toxicity after fast off-rate CD19 chimeric antigen receptor-T therapy in adults with relapsed or refractory B-cell acute lymphoblastic leukemia

.

J Clin Oncol

.

2021

;

39

(

30

):

3352

-

3363

.

12.

Hay

KA

,

Gauthier

J

,

Hirayama

AV

, et al.

Factors associated with durable EFS in adult B-cell ALL patients achieving MRD-negative CR after CD19 CAR T-cell therapy

.

Blood

.

2019

;

133

(

15

):

1652

-

1663

.

13.

Lee

DW

,

Kochenderfer

JN

,

Stetler-Stevenson

M

, et al.

T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trial

.

Lancet Lond Engl

.

2015

;

385

(

9967

):

517

-

528

.

14.

Ortiz-Maldonado

V

,

Rives

S

,

Español-Rego

M

, et al.

Factors associated with the clinical outcome of patients with relapsed/refractory CD19+ acute lymphoblastic leukemia treated with ARI-0001 CART19-cell therapy

.

J Immunother Cancer

.

2021

;

9

(

12

):

e003644

.

15.

Ghorashian

S

,

Kramer

AM

,

Onuoha

S

, et al.

Enhanced CAR T cell expansion and prolonged persistence in pediatric patients with ALL treated with a low-affinity CD19 CAR

.

Nat Med

.

2019

;

25

(

9

):

1408

-

1414

.

16.

Gardner

RA

,

Finney

O

,

Annesley

C

, et al.

Intent-to-treat leukemia remission by CD19 CAR T cells of defined formulation and dose in children and young adults

.

Blood

.

2017

;

129

(

25

):

3322

-

3331

.

17.

Laetsch

TW

,

Maude

SL

,

Rives

S

, et al.

Three-year update of tisagenlecleucel in pediatric and young adult patients with relapsed/refractory acute lymphoblastic leukemia in the ELIANA Trial

.

J Clin Oncol

.

2023

;

41

(

9

):

1664

-

1669

.

18.

Mueller

KT

,

Maude

SL

,

Porter

DL

, et al.

Cellular kinetics of CTL019 in relapsed/refractory B-cell acute lymphoblastic leukemia and chronic lymphocytic leukemia

.

Blood

.

2017

;

130

(

21

):

2317

-

2325

.

19.

Schultz

LM

,

Baggott

C

,

Prabhu

S

, et al.

Disease burden affects outcomes in pediatric and young adult B-cell lymphoblastic leukemia after commercial tisagenlecleucel: a Pediatric Real-World Chimeric Antigen Receptor Consortium Report

.

J Clin Oncol

.

2022

;

40

(

9

):

945

-

955

.

20.

Lee

DW

,

Santomasso

BD

,

Locke

FL

, et al.

ASBMT consensus grading for cytokine release syndrome and neurologic toxicity associated with immune effector cells

.

Biol Blood Marrow Transplant

.

2019;25(4):625-638

.

21.

Wayne

AS

,

Huynh

V

,

Hijiya

N

, et al.

Three-year results from phase I of ZUMA-4: KTE-X19 in pediatric relapsed/refractory acute lymphoblastic leukemia

.

Haematologica

.

2023

;

108

(

3

):

747

-

760

.

22.

Park

JH

,

Rivière

I

,

Gonen

M

, et al.

Long-term follow-up of CD19 CAR therapy in acute lymphoblastic leukemia

.

N Engl J Med

.

2018

;

378

(

5

):

449

-

459

.

23.

Turtle

CJ

,

Hanafi

LA

,

Berger

C

, et al.

CD19 CAR-T cells of defined CD4+:CD8+ composition in adult B cell ALL patients

.

J Clin Invest

.

2016

;

126

(

6

):

2123

-

2138

.

24.

Roloff

GW

,

Aldoss

I

,

Kopmar

NE

, et al.

Brexucabtagene autoleucel in adults with relapsed/refractory B-cell ALL: outcomes and novel insights from the Real-World Outcomes Collaborative of CAR T in Adult ALL (ROCCA) [abstract]

.

Blood

.

2023

;

142

(

suppl 1

):

1030

.

25.

Roloff

G

,

Faramand

R

,

Aldoss

I

, et al.

Outcomes following brexucabtagene autoleucel administered as an FDA-approved therapy for adults with relapsed/refractory B-ALL

.

J Clin Oncol

.

2023

;

41

(

16 suppl

):

7001

.

26.

Roddie

C

,

Pinto

JDA

,

O’Reilly

MA

.

Safety, efficiency and long-term follow-up of AUTO1, a fast-off rate CD19 CAR in relapsed/refractory B-cell acute lymphoblastic leukaemia and other B-cell malignancies [abstract]

.

Blood

.

2022

;

140

(

suppl 1

):

7452

-

7453

.

27.

Roddie

C

,

Sandhu

KS

,

Tholouli

E

, et al.

Obecabtagene autoleucel (obe-cel, AUTO1) for relapsed/refractory adult B-cell acute lymphoblastic leukemia (R/R B-ALL): pooled analysis of the ongoing FELIX phase Ib/II study [abstract]

.

Blood

.

2023

;

142

(

suppl 1

):

222

.

28.

Jabbour

E

,

Tholouli

E

,

Sandhu

KS

, et al.

Obecabtagene autoleucel (obe-cel, AUTO1) in adults with relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL): overall survival (OS), event-free survival (EFS) and the potential impact of chimeric antigen receptor (CAR)-T cell persistency and consolidative stem cell transplantation (SCT) in the open-label, single-arm FELIX phase Ib/II study [abstract]

.

J Clin Oncol

.

2024

;

42

(

16 suppl

):

6504

.

29.

Jacoby

E

,

Ghorashian

S

,

Vormoor

B

, et al.

CD19 CAR T-cells for pediatric relapsed acute lymphoblastic leukemia with active CNS involvement: a retrospective international study

.

Leukemia

.

2022

;

36

(

6

):

1525

-

1532

.

30.

Qi

Y

,

Zhao

M

,

Hu

Y

, et al.

Efficacy and safety of CD19-specific CAR T cell–based therapy in B-cell acute lymphoblastic leukemia patients with CNSL

.

Blood

.

2022

;

139

(

23

):

3376

-

3386

.

31.

Holland

EM

,

Yates

B

,

Ling

A

, et al.

Characterization of extramedullary disease in B-ALL and response to CAR T-cell therapy

.

Blood Adv

.

2022

;

6

(

7

):

2167

-

2182

.

32.

Zhang

X

,

Zhang

G

,

Li

W

, et al.

Factors associated with outcomes among refractory/relapsed TP53-mutated/chromosome 17p deletion acute B-cell lymphoblastic leukemia (B-ALL) patients treated with CD19-targeted chimeric antigen receptor (CAR)-T therapy [abstract]

.

Blood

.

2021

;

138

(

suppl 1

):

3828

.

33.

Pan

J

,

Tan

Y

,

Deng

B

, et al.

Frequent occurrence of CD19-negative relapse after CD19 CAR T and consolidation therapy in 14 TP53-mutated r/r B-ALL children

.

Leukemia

.

2020

;

34

(

12

):

3382

-

3387

.

34.

Mishra

AK

,

Burridge

S

,

Espuelas

MO

, et al.

Practice guideline: preparation for CAR T-cell therapy in children and young adults with B-acute lymphoblastic leukaemia

.

Br J Haematol

.

2024

;

204

(

5

):

1687

-

1696

.

35.

Feuchtinger

T

,

Bader

P

,

Subklewe

M

, et al.

Approaches for bridging therapy prior to chimeric antigen receptor T cells for relapsed/refractory acute lymphoblastic B-lineage leukemia in children and young adults

.

Haematologica

.

2024

;

109

(

12

):

3892

-

3903

.

36.

Rubinstein

JD

,

Breese

EH

,

Krupski

MC

, et al.

The choice of either conventional chemotherapy or inotuzumab ozogamicin as bridging regimen does not appear to impact clinical response to CD19-directed CAR-T therapy in pediatric B-ALL

.

Transplant Cell Ther

.

2023

;

29

(

5

):

311.e1

-

311.e7

.

37.

Ceolin

V

,

Brivio

E

,

van Tinteren

H

, et al.

Outcome of chimeric antigen receptor T-cell therapy following treatment with inotuzumab ozogamicin in children with relapsed or refractory acute lymphoblastic leukemia

.

Leukemia

.

2023

;

37

(

1

):

53

-

60

.

38.

Myers

RM

,

Taraseviciute

A

,

Steinberg

SM

, et al.

Blinatumomab nonresponse and high-disease burden are associated with inferior outcomes after CD19-CAR for B-ALL

.

J Clin Oncol

.

2022

;

40

(

9

):

932

-

944

.

39.

Fabrizio

VA

,

Boelens

JJ

,

Mauguen

A

, et al.

Optimal fludarabine lymphodepletion is associated with improved outcomes after CAR T-cell therapy

.

Blood Adv

.

2022

;

6

(

7

):

1961

-

1968

.

40.

Turtle

CJ

,

Hanafi

LA

,

Berger

C

, et al.

Addition of fludarabine to cyclophosphamide lymphodepletion improves in vivo expansion of CD19 chimeric antigen receptor-modified T cells and clinical outcome in adults with B cell acute lymphoblastic leukemia

.

Blood J

.

2015

;

126

(

23

):

3773

.

41.

Dekker

L

,

Calkoen

FG

,

Jiang

Y

, et al.

Fludarabine exposure predicts outcome after CD19 CAR T-cell therapy in children and young adults with acute leukemia

.

Blood Adv

.

2022

;

6

(

7

):

1969

-

1976

.

42.

Ghilardi

G

,

Chong

EA

,

Svoboda

J

, et al.

Bendamustine is safe and effective for lymphodepletion before tisagenlecleucel in patients with refractory or relapsed large B-cell lymphomas

.

Ann Oncol

.

2022

;

33

(

9

):

916

-

928

.

43.

Frey

NV

,

Shaw

PA

,

Hexner

EO

, et al.

Optimizing chimeric antigen receptor T-cell therapy for adults with acute lymphoblastic leukemia

.

J Clin Oncol

.

2020

;

38

(

5

):

415

-

422

.

44.

Frey

NV

,

Porter

DL

.

CAR T-cells merge into the fast lane of cancer care

.

Am J Hematol

.

2016

;

91

(

1

):

146

-

150

.

45.

Myers

RM

,

Kadauke

S

,

Li

Y

, et al.

Risk-adapted preemptive tocilizumab decreases severe cytokine release syndrome (CRS) after CTL019 CD19-targeted chimeric antigen receptor (CAR) T-cell therapy for pediatric B-cell acute lymphoblastic leukemia (B-ALL)

.

Biol Blood Marrow Transplant

.

2020

;

26

(

3

):

920

-

931

.

46.

Park

JH

,

Nath

K

,

Devlin

SM

, et al.

CD19 CAR T-cell therapy and prophylactic anakinra in relapsed or refractory lymphoma: phase 2 trial interim results

.

Nat Med

.

2023

;

29

(

7

):

1710

-

1717

.

47.

Mestermann

K

,

Giavridis

T

,

Weber

J

, et al.

The tyrosine kinase inhibitor dasatinib acts as a pharmacologic on/off switch for CAR T cells

.

Sci Transl Med

.

2019

;

11

(

499

):

eaau5907

.

48.

Weber

EW

,

Lynn

RC

,

Sotillo

E

,

Lattin

J

,

Xu

P

,

Mackall

CL

.

Pharmacologic control of CAR-T cell function using dasatinib

.

Blood Adv

.

2019

;

3

(

5

):

711

-

717

.

49.

Gu

C

,

Wu

Q

,

Zhang

J

, et al.

Successful treatment of severe cytokine release syndrome after CAR-T therapy by ruxolitinib without compromising CAR-T efficacy

.

Leuk Lymphoma

.

2023

;

64

(

2

):

495

-

498

.

50.

Frigault

MJ

,

Maziarz

RT

,

Park

JH

, et al.

Itacitinib for the prevention of immune effector cell therapy-associated cytokine release syndrome: results from the Phase 2 Incb 39110-211 placebo-controlled randomized cohort [abstract]

.

Blood

.

2023

;

142

(

suppl 1

):

356

.

51.

Sterner

RM

,

Sakemura

R

,

Cox

MJ

, et al.

GM-CSF inhibition reduces cytokine release syndrome and neuroinflammation but enhances CAR-T cell function in xenografts

.

Blood

.

2019

;

133

(

7

):

697

-

709

.

52.

Manni

S

,

Del Bufalo

F

,

Merli

P

, et al.

Neutralizing IFNγ improves safety without compromising efficacy of CAR-T cell therapy in B-cell malignancies

.

Nat Commun

.

2023

;

14

(

1

):

3423

.

53.

Zurko

JC

,

Johnson

BD

,

Aschenbrenner

E

, et al.

Use of early intrathecal therapy to manage high-grade immune effector cell-associated neurotoxicity syndrome

.

JAMA Oncol

.

2022

;

8

(

5

):

773

-

775

.

54.

Shalabi

H

,

Harrison

C

,

Yates

B

,

Calvo

KR

,

Lee

DW

,

Shah

NN

.

Intrathecal hydrocortisone for treatment of children and young adults with CAR T-cell immune-effector cell-associated neurotoxicity syndrome

.

Pediatr Blood Cancer

.

2024

;

71

(

1

):

e30741

.

55.

Kim

DW

,

Bukhari

A

,

Lutfi

F

, et al.

Low utility of the H-Score and HLH-2004 criteria to identify patients with secondary hemophagocytic lymphohistiocytosis after CAR-T cell therapy for relapsed/refractory diffuse large B-Cell lymphoma

.

Leuk Lymphoma

.

2022

;

63

(

6

):

1339

-

1347

.

56.

Lichtenstein

DA

,

Schischlik

F

,

Shao

L

, et al.

Characterization of HLH-like manifestations as a CRS variant in patients receiving CD22 CAR T cells

.

Blood

.

2021

;

138

(

24

):

2469

-

2484

.

57.

Jain

T

,

Knezevic

A

,

Pennisi

M

, et al.

Hematopoietic recovery in patients receiving chimeric antigen receptor T-cell therapy for hematologic malignancies

.

Blood Adv

.

2020

;

4

(

15

):

3776

-

3787

.

58.

O’Reilly

MA

,

Neill

L

,

Collin

SM

, et al.

High pretreatment disease burden as a risk factor for infectious complications following CD19 chimeric antigen receptor T-cell therapy for large B-cell lymphoma

.

HemaSphere

.

2024

;

8

(

1

):

e29

.

59.

Haidar

G

,

Garner

W

,

Hill

JA

.

Infections after anti-CD19 chimeric antigen receptor T-cell therapy for hematologic malignancies: timeline, prevention, and uncertainties

.

Curr Opin Infect Dis

.

2020

;

33

(

6

):

449

-

457

.

60.

Hayden

PJ

,

Roddie

C

,

Bader

P

, et al.

Management of adults and children receiving CAR T-cell therapy: 2021 best practice recommendations of the European Society for Blood and Marrow Transplantation (EBMT) and the Joint Accreditation Committee of ISCT and EBMT (JACIE) and the European Haematology Association (EHA)

.

Ann Oncol

.

2022;33(3):259-275

.

61.

Verdun

N

,

Marks

P

.

Secondary cancers after chimeric antigen receptor T-cell therapy

.

N Engl J Med

.

2024

;

390

(

7

):

584

-

586

.

62.

Hamilton

MP

,

Sugio

T

,

Noordenbos

T

, et al.

Risk of second tumors and T-cell lymphoma after CAR T-cell therapy

.

N Engl J Med

.

2024

;

390

(

22

):

2047

-

2060

.

63.

Lamble

AJ

,

Schultz

LM

,

Nguyen

K

, et al.

Risk of T-cell malignancy after CAR T-cell therapy in children, adolescents, and young adults

.

Blood Adv

.

2024

;

8

(

13

):

3544

-

3548

.

64.

Ozdemirli

M

,

Loughney

TM

,

Deniz

E

, et al.

Indolent CD4+ CAR T-cell lymphoma after cilta-cel CAR T-cell therapy

.

N Engl J Med

.

2024

;

390

(

22

):

2074

-

2082

.

65.

Ghilardi

G

,

Fraietta

JA

,

Gerson

JN

, et al.

T cell lymphoma and secondary primary malignancy risk after commercial CAR T cell therapy

.

Nat Med

.

2024

;

30

(

4

):

984

-

989

.

66.

Shiqi

L

,

Jiasi

Z

,

Lvzhe

C

, et al.

Durable remission related to CAR-T persistence in R/R B-ALL and long-term persistence potential of prime CAR-T

.

Mol Ther Oncolytics

.

2023

;

29

:

107

-

117

.

67.

Turicek

DP

,

Giordani

VM

,

Moraly

J

,

Taylor

N

,

Shah

NN

.

CAR T-cell detection scoping review: an essential biomarker in critical need of standardization

.

J Immunother Cancer

.

2023

;

11

(

5

):

e006596

.

68.

Gkazi

SA

,

Gravett

E

,

Bautista

C

,

Bartram

J

,

Ghorashian

S

,

Adams

SP

.

Clinically applicable assessment of tisagenlecleucel CAR T cell treatment by digital droplet PCR for copy number variant assessment

.

Int J Mol Sci

.

2022

;

23

(

14

):

7573

.

69.

Pulsipher

MA

,

Han

X

,

Maude

SL

, et al.

Next-generation sequencing of minimal residual disease for predicting relapse after tisagenlecleucel in children and young adults with acute lymphoblastic leukemia

.

Blood Cancer Discov

.

2022

;

3

(

1

):

66

-

81

.

70.

Dourthe

ME

,

Rabian

F

,

Yakouben

K

, et al.

Determinants of CD19-positive vs CD19-negative relapse after tisagenlecleucel for B-cell acute lymphoblastic leukemia

.

Leukemia

.

2021

;

35

(

12

):

3383

-

3393

.

71.

Lamble

AJ

,

Moskop

A

,

Pulsipher

MA

, et al.

INSPIRED Symposium Part 2: Prevention and Management of Relapse Following Chimeric Antigen Receptor T Cell Therapy for B Cell Acute Lymphoblastic Leukemia

.

Transplant Cell Ther

.

2023

;

29

(

11

):

674

-

684

.

72.

Ganzel

C

,

Wang

XV

,

Rowe

JM

, et al.

At three years, patients with acute lymphoblastic leukaemia are still at risk for relapse. Results of the international MRC UKALLXII/ECOG E2993 trial

.

Br J Haematol

.

2020

;

191

(

1

):

37

-

43

.

73.

Biasco

L

,

Izotova

N

,

Rivat

C

, et al.

Clonal expansion of T memory stem cells determines early anti-leukemic responses and long-term CAR T cell persistence in patients

.

Nat Can (Ott)

.

2021

;

2

(

6

):

629

-

642

.

74.

Finney

OC

,

Brakke

HM

,

Rawlings-Rhea

S

, et al.

CD19 CAR T cell product and disease attributes predict leukemia remission durability

.

J Clin Invest

.

2019

;

129

(

5

):

2123

-

2132

.

75.

Leahy

AB

,

Devine

KJ

,

Li

Y

, et al.

Impact of high-risk cytogenetics on outcomes for children and young adults receiving CD19-directed CAR T-cell therapy

.

Blood

.

2022

;

139

(

14

):

2173

-

2185

.

76.

Myers

RM

,

Taraseviciute

A

,

Steinberg

SM

, et al.

Blinatumomab nonresponse and high-disease burden are associated with inferior outcomes after CD19-CAR for B-ALL

.

J Clin Oncol

.

2021

;

40(9):932-945

.

77.

Gabelli

M

,

Oporto-Espuelas

M

,

Bonney

DK

, et al.

Maintenance therapy for early loss of B-cell aplasia after CD19 CAR T-cell therapy

.

Blood Adv

.

2024;8(8):1959-1963

.

78.

Pan

J

,

Yang

JF

,

Deng

BP

, et al.

High efficacy and safety of low-dose CD19-directed CAR-T cell therapy in 51 refractory or relapsed B acute lymphoblastic leukemia patients

.

Leukemia

.

2017

;

31

(

12

):

2587

-

2593

.

79.

Shadman

M

,

Gauthier

J

,

Hay

KA

, et al.

Safety of allogeneic hematopoietic cell transplant in adults after CD19-targeted CAR T-cell therapy

.

Blood Adv

.

2019

;

3

(

20

):

3062

-

3069

.

80.

Nagler

A

,

Labopin

M

,

Dholaria

B

, et al.

Second allogeneic stem cell transplantation in patients with acute lymphoblastic leukaemia: a study on behalf of the Acute Leukaemia Working Party of the European Society for Blood and Marrow Transplantation

.

Br J Haematol

.

2019

;

186

(

5

):

767

-

776

.

81.

Chen

LY

,

Gong

WJ

,

Li

MH

, et al.

Anti-CD19 CAR T-cell consolidation therapy combined with CD19+ feeding T cells and TKI for Ph+ acute lymphoblastic leukemia

.

Blood Adv

.

2023

;

7

(

17

):

4913

-

4925

.

82.

Cassaday

RD

,

Garcia

KLA

,

Fromm

JR

, et al.

Phase 2 study of pembrolizumab for measurable residual disease in adults with acute lymphoblastic leukemia

.

Blood Adv

.

2020

;

4

(

14

):

3239

-

3245

.

83.

Li

AM

,

Hucks

GE

,

Dinofia

AM

, et al.

Checkpoint inhibitors augment CD19-directed chimeric antigen receptor (CAR) T cell therapy in relapsed B-cell acute lymphoblastic leukemia [abstract]

.

Blood

.

2018

;

132

(

suppl 1

):

556

.

84.

Elsallab

M

,

Ellithi

M

,

Hempel

S

,

Abdel-Azim

H

,

Abou-el-Enein

M

.

Long-term response to autologous anti-CD19 chimeric antigen receptor T cells in relapsed or refractory B cell acute lymphoblastic leukemia: a systematic review and meta-analysis

.

Cancer Gene Ther

.

2023

;

30

(

6

):

845

-

854

.

85.

Sun

W

,

Malvar

J

,

Sposto

R

, et al.

Outcome of children with multiply relapsed B-cell acute lymphoblastic leukemia: a Therapeutic Advances in Childhood Leukemia & Lymphoma study

.

Leukemia

.

2018

;

32

(

11

):

2316

-

2325

.

86.

Wudhikarn

K

,

King

AC

,

Geyer

MB

, et al.

Outcomes of relapsed B-cell acute lymphoblastic leukemia after sequential treatment with blinatumomab and inotuzumab

.

Blood Adv

.

2022

;

6

(

5

):

1432

-

1443

.

87.

Sotillo

E

,

Barrett

DM

,

Black

KL

, et al.

Convergence of acquired mutations and alternative splicing of CD19 enables resistance to CART-19 immunotherapy

.

Cancer Discov

.

2015

;

5

(

12

):

1282

-

1295

.

88.

Fry

TJ

,

Shah

NN

,

Orentas

RJ

, et al.

CD22-targeted CAR T cells induce remission in B-ALL that is naive or resistant to CD19-targeted CAR immunotherapy

.

Nat Med

.

2018

;

24

(

1

):

20

-

28

.

89.

Shah

NN

,

Highfill

SL

,

Shalabi

H

, et al.

CD4/CD8 T-cell selection affects chimeric antigen receptor (CAR) T-cell potency and toxicity: updated results from a phase I Anti-CD22 CAR T-Cell Trial

.

J Clin Oncol

.

2020

;

38

(

17

):

1938

-

1950

.

90.

Pan

J

,

Niu

Q

,

Deng

B

, et al.

CD22 CAR T-cell therapy in refractory or relapsed B acute lymphoblastic leukemia

.

Leukemia

.

2019

;

33

(

12

):

2854

-

2866

.

91.

Schultz

LM

,

Jeyakumar

N

,

Kramer

AM

, et al.

CD22 CAR T cells demonstrate high response rates and safety in pediatric and adult B-ALL: phase 1b results

.

Leukemia

.

2024

;

38

(

5

):

963

-

968

.

92.

Cordoba

S

,

Onuoha

S

,

Thomas

S

, et al.

CAR T cells with dual targeting of CD19 and CD22 in pediatric and young adult patients with relapsed or refractory B cell acute lymphoblastic leukemia: a phase 1 trial

.

Nat Med

.

2021

;

27

(

10

):

1797

-

1805

.

93.

Shalabi

H

,

Qin

H

,

Su

A

, et al.

CD19/22 CAR T-cells in children and young adults with B-ALL: phase I results and development of a novel bicistronic CAR

.

Blood

.

2022;140(5):451-463

.

94.

Spiegel

JY

,

Patel

S

,

Muffly

L

, et al.

T cells with dual targeting of CD19 and CD22 in adult patients with recurrent or refractory B cell malignancies: a phase 1 trial

.

Nat Med

.

2021

;

27

(

8

):

1416

-

1431

.

95.

Gardner

R

,

Annesley

C

,

Finney

O

, et al.

Early clinical experience of CD19 x CD22 dual specific CAR T cells for enhanced anti-leukemic targeting of acute lymphoblastic leukemia [abstract]

.

Blood

.

2018

;

132

(

suppl 1

):

278

.

96.

Annesley

C

,

Summers

C

,

Pulsipher

MA

, et al.

SCRI-CAR19x22v2 T cell product demonstrates bispecific activity in B-ALL [abstract]

.

Blood

.

2021

;

138

(

suppl 1

):

470

.

97.

Ghorashian

S

,

Lucchini

G

,

Richardson

R

, et al.

CD19/CD22 targeting with cotransduced CAR T cells to prevent antigen-negative relapse after CAR T-cell therapy for B-cell ALL

.

Blood

.

2024

;

143

(

2

):

118

-

123

.

98.

Wang

T

,

Tang

Y

,

Cai

J

, et al.

Coadministration of CD19- and CD22-directed chimeric antigen receptor T-cell therapy in childhood B-cell acute lymphoblastic leukemia: a single-arm, multicenter, phase II trial

.

J Clin Oncol

.

2023

;

41

(

9

):

1670

-

1683

.

99.

Pan

J

,

Tang

K

,

Luo

Y

, et al.

Sequential CD19 and CD22 chimeric antigen receptor T-cell therapy for childhood refractory or relapsed B-cell acute lymphocytic leukaemia: a single-arm, phase 2 study

.

Lancet Oncol

.

2023

;

24

(

11

):

1229

-

1241

.

100.

Gauthier

J

,

Bezerra

ED

,

Hirayama

AV

, et al.

Factors associated with outcomes after a second CD19-targeted CAR T-cell infusion for refractory B-cell malignancies

.

Blood

.

2021

;

137

(

3

):

323

-

335

.

101.

Holland

EM

,

Molina

JC

,

Dede

K

, et al.

Efficacy of second CAR-T (CART2) infusion limited by poor CART expansion and antigen modulation

.

J Immunother Cancer

.

2022

;

10

(

5

):

e004483

.

102.

Xu

Q

,

Shi

Y

,

Xue

L

, et al.

Outcomes of second anti-CD19 CAR T-cell therapy (CART2) in acute B lymphoblastic leukemia and the impact of Allo-HSCT on efficacy

.

Cell Transplant

.

2023

;

32

:

09636897231204724

.

103.

Myers

RM

,

Li

Y

,

Barz Leahy

A

, et al.

Humanized CD19-targeted chimeric antigen receptor (CAR) T cells in CAR-naive and CAR-exposed children and young adults with relapsed or refractory acute lymphoblastic leukemia

.

J Clin Oncol

.

2021

;

39

(

27

):

3044

-

3055

.

104.

Zarebski

LM

,

Urrutia

M

,

Goldbaum

FA

.

Llama single domain antibodies as a tool for molecular mimicry

.

J Mol Biol

.

2005

;

349

(

4

):

814

-

824

.

105.

Sun

Y

,

Yang

XN

,

Yang

SS

, et al.

Antigen-induced chimeric antigen receptor multimerization amplifies on-tumor cytotoxicity

.

Signal Transduct Targeted Ther

.

2023

;

8

(

1

):

445

. 12.

106.

Benjamin

R

,

Jain

N

,

Maus

MV

, et al;

CALM Study Group

.

UCART19, a first-in-class allogeneic anti-CD19 chimeric antigen receptor T-cell therapy for adults with relapsed or refractory B-cell acute lymphoblastic leukaemia (CALM): a phase 1, dose-escalation trial

.

Lancet Haematol

.

2022

;

9

(

11

):

e833

-

e843

.

107.

Depil

S

,

Duchateau

P

,

Grupp

SA

,

Mufti

G

,

Poirot

L

.

‘Off-the-shelf’ allogeneic CAR T cells: development and challenges

.

Nat Rev Drug Discov

.

2020

;

19

(

3

):

185

-

199

.

108.

Chattaraj

A

,

Rehman

MEU

,

Khan

I

, et al.

Safety and efficacy of allogeneic CAR-T cells in B-cell malignancies: a systematic review and meta-analysis

.

J Clin Oncol

.

2022

;

40

(

16 suppl

):

e19530

.

109.

Yang

J

,

He

J

,

Zhang

X

, et al.

Next-day manufacture of a novel anti-CD19 CAR-T therapy for B-cell acute lymphoblastic leukemia: first-in-human clinical study

.

Blood Cancer J

.

2022

;

12

(

7

):

104

.

110.

Klebanoff

CA

,

Crompton

JG

,

Leonardi

AJ

, et al.

Inhibition of AKT signaling uncouples T cell differentiation from expansion for receptor-engineered adoptive immunotherapy

.

JCI Insight

.

2017

;

2

(

23

):

e95103

.

111.

Mehra

V

,

Agliardi

G

,

Dias Alves Pinto

J

, et al.

AKT inhibition generates potent polyfunctional clinical grade AUTO1 CAR T-cells, enhancing function and survival

.

J Immunother Cancer

.

2023

;

11

(

9

):

e007002

.

112.

Di

M

,

Long

JB

,

Isufi

I

, et al.

Total costs of care during chimeric antigen receptor T-cell therapy in patients with relapsed/refractory B cell non-Hodgkin lymphoma: a large private insurance claim-based analysis [abstract]

.

Blood

.

2022

;

140

(

suppl 1

):

10818

-

10819

.

113.

Castella

M

,

Boronat

A

,

Martín-Ibáñez

R

, et al.

Development of a novel anti-CD19 chimeric antigen receptor: a paradigm for an affordable CAR T cell production at academic institutions

.

Mol Ther Methods Clin Dev

.

2019

;

12

:

134

-

144

.

114.

Mallapaty

S

.

Cutting-edge CAR-T cancer therapy is now made in India — at one-tenth the cost

.

Nature

.

2024

;

627

(

8005

):

709

-

710

.

115.

Neelapu

SS

,

Dickinson

M

,

Munoz

J

, et al.

Axicabtagene ciloleucel as first-line therapy in high-risk large B-cell lymphoma: the phase 2 ZUMA-12 trial

.

Nat Med

.

2022

;

28

(

4

):

735

-

742

.