CD19 CAR T cells are an effective therapy for posttransplant relapse in patients with B-lineage ALL: real-world data from Germany

被引：34

作者：

Bader, Peter ^{[1
]}

Rossig, Claudia ^{[2
]}

Hutter, Martin ^{[1
]}

Ayuk, Francis Ayuketang ^{[3
]}

Baldus, Claudia D. ^{[4
]}

Buecklein, Veit L. ^{[5
]}

Bonig, Halvard ^{[6
,7
]}

Cario, Gunnar ^{[8
]}

Einsele, Hermann ^{[9
]}

Holtick, Udo ^{[10
,11
]}

Koenecke, Christian ^{[12
]}

Bakhtiar, Shahrzad ^{[1
]}

Kuenkele, Annette ^{[13
,14
,15
]}

Meisel, Roland ^{[16
]}

Mueller, Fabian ^{[17
]}

Mueller, Ingo ^{[18
]}

Penack, Olaf ^{[14
,15
,19
]}

Rettinger, Eva ^{[1
]}

Sauer, Martin G. ^{[20
]}

Schlegel, Paul -Gerhardt ^{[21
]}

Soerensen, Jan ^{[1
]}

von Stackelberg, Arend ^{[13
]}

Strahm, Brigitte ^{[22
]}

Hauer, Julia ^{[23
,24
]}

Feuchtinger, Tobias ^{[25
]}

Jarisch, Andrea ^{[1
]}

机构：

[1] Goethe Univ, Univ Hosp, Dept Children & Adolescents, Div Stem Cell Transplantat Immunol & Intens Care, Frankfurt, Germany

[2] Muenster Univ, Pediat Hematol & Oncol, Childrens Hosp, Munster, Germany

[3] Hamburg Eppendorf Univ, Dept Stem Cell Transplantat, Med Ctr, Hamburg, Germany

[4] Schleswig Holstein Univ Hosp, Dept Internal Med 2, Kiel, Germany

[5] Ludwig Maximilian Univ Munich, Univ Hosp, Dept Med 3, Munich, Germany

[6] Goethe Univ, Translat Dev Cellular Therapies, Inst Transfus Med & lmmunohematol, Frankfurt, Germany

[7] German Red Cross Blood Serv Baden Wurttemberg Hes, Frankfurt, Hessen, Germany

[8] Univ Med Ctr Schleswig Holstein, Dept Pediat, Campus Kiel, Kiel, Germany

[9] Univ Hosp Wuerzburg, Dept Med 2, Wurzburg, Germany

[10] Univ Cologne, Med Fac, Dept Internal Med 1, Cologne, Germany

[11] Univ Cologne, Univ Hosp Cologne, Cologne, Germany

[12] Hannover Med Sch, Dept Hematol Hemostasis Oncol & Stem Cell Transpl, Hannover, Germany

[13] Charit Univ Med Berlin, Dept Pediat Oncol & Hematol, Berlin, Germany

[14] Free Univ Berlin, Berlin, Germany

[15] Humboldt Univ, Berlin, Germany

[16] Heinrich Heine Univ, Med Fac, Dept Pediat Oncol Hematol & Clin lmmunol, Div Pediat Stem Cell Therapy, Dusseldorf, Germany

[17] Friedrich Alexander Univ Erlangen Nurnberg FAU, Univ Hosp Erlangen, Dept Internal Med Haematol & Oncol 5, Erlangen, Germany

[18] Hamburg Eppendorf Univ, Div Pediat Stem Cell Transplantat & Immunol, Med Ctr, Hamburg, Germany

[19] Charite Univ Med Berlin, Dept Hematol Oncol & Tumorimmunol, Berlin, Germany

[20] Hannover Med Sch, Pediat Hematol & Oncol, Hannover, Germany

[21] Wuerzburg Univ, Dept Pediat Hematol Oncol Stem Cell Transplantat, Childrens Hosp, Wurzburg, Germany

[22] Univ Freiburg, Fac Med, Med Ctr, Dept Pediat & Adolescent Med, Freiburg, Germany

[23] Tech Univ Dresden, Univ Hosp Carl Gustav Carus, Dept Pediat Pediat Hematol & Oncol, Dresden, Germany

[24] Tech Univ Munich, Childrens Canc Res Ctr, Sch Med, Dept Pediat,Kinderklin Munchen Schwabing, Munich, Germany

[25] Ludwig Maximilian Univ Munich, Dr von Hauner Childrens Hosp, Dept Pediat Hematol Oncol & Stem Cell Transplanta, Munich, Germany

来源：

BLOOD ADVANCES | 2023年 / 7卷 / 11期

关键词：

ACUTE LYMPHOBLASTIC-LEUKEMIA; CHILDREN; CHILDHOOD; TISAGENLECLEUCEL; TRANSPLANTATION; ADOLESCENTS; OUTCOMES;

D O I：

10.1182/bloodadvances.2022008981

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Patients with precursor B-cell acute lymphoblastic leukemia (pB-ALL) who have relapsed after allogeneic hematopoietic stem cell transplantation (allo-HSCT), have relapsed more than once, or are resistant upfront have a dismal prognosis. CD19-targeted chimeric antigen receptor (CAR) T cells have evolved as potent immune therapies. Tisagenlecleucel (Tisa-cel) is a commercially available autologous CD19-directed CAR T-cell product. We performed a retrospective study inviting all CAR T-cell centers in Germany to participate. Eighty-one patients with pB-ALL were included. Twenty-eight days after CAR T-cell infusion, 71 patients (87.7%) were in complete response, and 8 (9.9%) were in nonremission. At 2 years, the probabilities of event-free survival (pEFS), relapse-free survival (pRFS), and overall survival (pOS) were 45.3%, 51.7%, and 53.2%, respectively. pEFS was not different in patients without (n = 16, 55.0%) vs with prior allo-HSCT (n = 65, 43.4%). In patients treated after allo-HSCT, the time to relapse after allo-HSCT was a strong predictor of outcome. Patients relapsing within 6 months of allo-HSCT had a disappointing pEFS of 18.4% (pOS = 16.0%); the pEFS for those relapsing later was 55.5% (pOS = 74.8%). Our study provides real-world experience in pediatric, adolescent, and young adult patients with ALL treated with Tisa-cel, where most patients were treated after having relapsed after allo-HSCT. A total of 45.3% were rescued with a single dose of Tisa-cel. Our novel finding that patients with ALL after allo-HSCT had by far a better pEFS if relapse occurred beyond 6 months might be helpful in clinical decision-making and motivates studies to uncover the reasons.

引用

页码：2436 / 2448

页数：13

共 32 条

[31] Second Hematopoietic Stem Cell Transplantation for Post-Transplantation Relapsed Acute Leukemia in Children: A Retrospective EBMT-PDWP Study [J].

Yaniv, Isaac ;

Krauss, Aviva C. ;

Beohou, Eric ;

Dalissier, Arnaud ;

Corbacioglu, Selim ;

Zecca, Marco ;

Afanasyev, Boris V. ;

Berger, Massimo ;

Angel Diaz, Miguel ;

Kalwak, Krzysztof ;

Sedlacek, Petr ;

Varotto, Stefania ;

Peters, Christina ;

Bader, Peter .

BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION, 2018, 24 (08) :1629-1642

[32] Efficacy and safety of anti-CD19 CAR T-cell therapy in 110 patients with B-cell acute lymphoblastic leukemia with high-risk features [J].

Zhang, Xian ;

Lu, Xin-an ;

Yang, Junfang ;

Zhang, Gailing ;

Li, Jingjing ;

Song, Lisong ;

Su, Yunchao ;

Shi, Yanze ;

Zhang, Min ;

He, Jiujiang ;

Song, Dan ;

Lv, Fanyong ;

Li, Wenqian ;

Wu, Yan ;

Wang, Hui ;

Liu, Hongxing ;

Zhou, Xiaosu ;

He, Ting ;

Lu, Peihua .

BLOOD ADVANCES, 2020, 4 (10) :2325-2338

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