Skip to main content
Key Specialties
Anesthesiology Cardiology Dermatology Diabetology Endocrinology Gastroenterology and Hepatology General Medicine Geriatrics Hematology Infectious Diseases Internal Medicine Nephrology Neurology Obstetrics and Gynecology Oncology Ophthalmology Pediatrics Psychiatry Radiology Respiratory Medicine Rheumatology Surgery Urology
Congress Coverage
ASH 2024 Annual Meeting 2024 ESMO Congress 2024 ERS Congress 2024 EASD Congress 2024 ESC Congress 2024 EAN Congress 2024 ASCO Annual Meeting 2024 ACC Congress
Clinical Collections
Advances in Alzheimer’s

Podcast | Sexual health in older age

Dr Holly Thomas helps us unpack the needlessly taboo subject of sex and sexual health in women of older age.

Listen now
ADVANCED SEARCH
Log in
Top
Annals of Hematology
Published in:

18-12-2024 | CAR T-Cell Therapy | Review

Clinical outcomes and safety of CAR-T cells in treatment of T-Cell acute lymphoblastic leukemia/lymphoma

Authors: Jin-Feng Ma, Chun-Long Yan, Xu Jia, Hong-Jia Zhu, Jia-Wei Yan, Mei-Jing Liu, Dai-Yi Zhang, Shen-Hao Liu, Nan Xu, Hai-Guo Zhang, Ling Ye, Lei Yu, De-Pei Wu, Wen-Jie Gong, Hai-Ping Dai, Sheng-Li Xue

Published in: Annals of Hematology | Issue 1/2025

Login to get access

Abstract

Relapsed or refractory T-cell acute lymphoblastic leukemia/lymphoma (r/r T-ALL/LBL) are frequently aggressive and associated with unfavorable prognoses. Pan-targeted Chimeric Antigen Receptor (CAR) T-cell therapy have shown promising results in clinical trials. In recent years, CD7 CAR T-cell and CD5 CAR T-cell demonstrate effectiveness in treating r/r T-ALL/LBL patients with bone marrow infiltration. However, nearly half of r/r T-ALL/T-LBL patients are accompanied by extramedullary disease (EMD), where comprehensive data on the efficacy and safety of CAR T-cell therapy remain limited. Additionally, CD7 CAR T-cell and CD5 CAR T-cell therapy can cause severe immunodeficiency and hematologic toxicity, complicating with difficult immune reconstitution. This review provides an in-depth analysis of the safety profile and adverse events associated with CAR T-cell therapy in r/r T-ALL/LBL, with a a particular emphasis on its impact in patients with EMD.
Literature
1.
Sánchez-Martínez D, Baroni ML, Gutierrez-Agüera F, Roca-Ho H, Blanch-Lombarte O, González-García S et al (2019) Fratricide-resistant CD1a-specific CAR T cells for the treatment of cortical T-cell acute lymphoblastic leukemia. Blood 133(21):2291–2304PubMedPubMedCentral
2.
Tong C, Zhang Y, Liu Y, Ji X, Zhang W, Guo Y et al (2020) Optimized tandem CD19/CD20 CAR-engineered T cells in refractory/relapsed B-cell lymphoma. Blood 136(14):1632–1644PubMedPubMedCentral
3.
Ma JF, Yan JW, Liu MJ, Yan CL, Tang XW, Qiu HY et al (2024) Safe and potent anti-CD19 CAR T-cells with shRNA-IL-6 gene silencing element in patients with refractory or relapsed B-cell acute lymphoblastic leukemia. Hemasphere 8(10):e70007PubMedPubMedCentral
4.
Winter SS, Dunsmore KP, Devidas M, Wood BL, Esiashvili N, Chen Z et al (2018) Improved survival for children and young adults with t-lineage acute lymphoblastic leukemia: results from the children’s oncology group AALL0434 methotrexate randomization. J Clin Oncol 36(29):2926–2934PubMedPubMedCentral
5.
Marks DI, Paietta EM, Moorman AV, Richards SM, Buck G, DeWald G et al (2009) T-cell acute lymphoblastic leukemia in adults: clinical features, immunophenotype, cytogenetics, and outcome from the large randomized prospective trial (UKALL XII/ECOG 2993). Blood 114(25):5136–5145PubMedPubMedCentral
6.
Goldberg JM, Silverman LB, Levy DE, Dalton VK, Gelber RD, Lehmann L et al (2003) Childhood T-cell acute lymphoblastic leukemia: the Dana-Farber Cancer Institute acute lymphoblastic leukemia consortium experience. J Clin Oncol 21(19):3616–3622PubMed
7.
Mamonkin M, Rouce RH, Tashiro H, Brenner MK (2015) A T-cell-directed chimeric antigen receptor for the selective treatment of T-cell malignancies. Blood 126(8):983–992PubMedPubMedCentral
8.
Cooper ML, Choi J, Staser K, Ritchey JK, Devenport JM, Eckardt K et al (2018) An “off-the-shelf” fratricide-resistant CAR-T for the treatment of T cell hematologic malignancies. Leukemia 32(9):1970–1983PubMedPubMedCentral
9.
Rasaiyaah J, Georgiadis C, Preece R, Mock U, Qasim W (2018) TCRαβ/CD3 disruption enables CD3-specific antileukemic T cell immunotherapy. JCI Insight 3(13):e99442PubMedPubMedCentral
10.
Li S, Wang X, Yuan Z, Liu L, Luo L, Li Y et al (2021) Eradication of T-ALL Cells by CD7-targeted Universal CAR-T Cells and Initial Test of Ruxolitinib-based CRS Management. Clin Cancer Res 27(5):1242–1246PubMed
11.
Pan J, Tan Y, Wang G, Deng B, Ling Z, Song W et al (2021) Donor-Derived CD7 Chimeric Antigen Receptor T Cells for T-Cell Acute Lymphoblastic Leukemia: First-in-Human. Phase I Trial J Clin Oncol 39(30):3340–3351PubMed
12.
Pan J, Tan Y, Shan L, Deng B, Ling Z, Song W et al (2022) Phase I study of donor-derived CD5 CAR T cells in patients with relapsed or refractory T-cell acute lymphoblastic leukemia. J Clin Oncol 40(16_suppl):7028
13.
Marks DI, Rowntree C (2017) Management of adults with T-cell lymphoblastic leukemia. Blood 129(9):1134–1142PubMed
14.
Teachey DT, Pui CH (2019) Comparative features and outcomes between paediatric T-cell and B-cell acute lymphoblastic leukaemia. Lancet Oncol 20(3):e142–e154PubMedPubMedCentral
15.
Yang J, Yang X, Liu Y, Wang Q, Wang H, Li J et al (2021) A novel and successful patient or donor-derived CD7-Targeted CAR T-Cell therapy for relapsed or refractory T-Cell lymphoblastic lymphoma (R/R T-LBL). Blood 138(Supplement 1):652
16.
Tan Y, Shan L, Zhao L, Deng B, Ling Z, Zhang Y et al (2023) Long-term follow-up of donor-derived CD7 CAR T-cell therapy in patients with T-cell acute lymphoblastic leukemia. J Hematol Oncol 16(1):34PubMedPubMedCentral
17.
Zhang M, Chen D, Fu X, Meng H, Nan F, Sun Z et al (2022) Autologous nanobody-derived fratricide-resistant CD7-CAR T-cell therapy for patients with relapsed and refractory T-cell acute lymphoblastic leukemia/lymphoma. Clin Cancer Res 28(13):2830–2843PubMed
18.
Zhang X, Yang J, Li J, Qiu L, Li J, Lu P (2022) Analysis of 53 Patients with Relapsed or Refractory (R/R) T-Cell Acute Lymphoblastic Leukemia (T-ALL) and T-Cell Lymphoblastic Lymphoma (T-LBL) Treated with CD7-Targeted CAR-T Cell Therapy. Blood 140(Supplement 1):2369–2370
19.
Chen W, Shi H, Liu Z, Yang F, Liu J, Zhang L et al (2023) Single-Cell Transcriptomics Reveals Immune Reconstitution in Patients with R/R T-ALL/LBL Treated with Donor-Derived CD7 CAR-T Therapy. Clin Cancer Res 29(8):1484–1495PubMed
20.
Hu Y, Zhou Y, Zhang M, Zhao H, Wei G, Ge W et al (2022) Genetically modified CD7-targeting allogeneic CAR-T cell therapy with enhanced efficacy for relapsed/refractory CD7-positive hematological malignancies: a phase I clinical study. Cell Res 32(11):995–1007PubMedPubMedCentral
21.
Vitale A, Guarini A, Ariola C, Mancini M, Mecucci C, Cuneo A et al (2006) Adult T-cell acute lymphoblastic leukemia: biologic profile at presentation and correlation with response to induction treatment in patients enrolled in the GIMEMA LAL 0496 protocol. Blood 107(2):473–479PubMed
22.
Li Z, An N, Yang K, Meng F, Xu T, Peng X et al (2023) Donor CD7 chimeric antigen receptor T cell bridging to allogeneic hematopoietic stem cell transplantation for T cell hematologic malignancy. Transplant Cell Ther 29(3):167–173PubMed
23.
Zhang Y, Li C, Du M, Jiang H, Luo W, Tang L et al (2023) Allogenic and autologous anti-CD7 CAR-T cell therapies in relapsed or refractory T-cell malignancies. Blood Cancer J 13(1):61PubMedPubMedCentral
24.
Lu P, Liu Y, Yang J, Zhang X, Yang X, Wang H et al (2022) Naturally selected CD7 CAR-T therapy without genetic manipulations for T-ALL/LBL: first-in-human phase 1 clinical trial. Blood 140(4):321–334PubMed
25.
Zhao L, Pan J, Tang K, Tan Y, Deng B, Ling Z et al (2022) Autologous CD7-targeted CAR T-cell therapy for refractory or relapsed T-cell acute lymphoblastic leukemia/lymphoma. J Clin Oncol 40(16_suppl):7035
26.
Dai HP, Cui W, Cui QY, Zhu WJ, Meng HM, Zhu MQ et al (2022) Haploidentical CD7 CAR T-cells induced remission in a patient with TP53 mutated relapsed and refractory early T-cell precursor lymphoblastic leukemia/lymphoma. Biomark Res 10(1):6PubMedPubMedCentral
27.
Zhang X, Zhou Y, Yang J, Li J, Qiu L, Ge W et al (2022) A Novel Universal CD7-Targeted CAR-T Cell Therapy for Relapsed or Refractory T-Cell Acute Lymphoblastic Leukemia and T-Cell Lymphoblastic Lymphoma. Blood 140(Supplement 1):4566–4567
28.
Maude SL, Laetsch TW, Buechner J, Rives S, Boyer M, Bittencourt H et al (2018) Tisagenlecleucel in children and young adults with B-Cell Lymphoblastic Leukemia. N Engl J Med 378(5):439–448PubMedPubMedCentral
29.
Rabinowich H, Pricop L, Herberman RB, Whiteside TL (1994) Expression and function of CD7 molecule on human natural killer cells. J Immunol 152(2):517–526PubMed
30.
Aandahl EM, Sandberg JK, Beckerman KP, Taskén K, Moretto WJ, Nixon DF (2003) CD7 is a differentiation marker that identifies multiple CD8 T cell effector subsets. J Immunol 170(5):2349–2355PubMed
31.
Pol JG, Caudana P, Paillet J, Piaggio E, Kroemer G (2020) Effects of interleukin-2 in immunostimulation and immunosuppression. J Exp Med 217(1):e20191247PubMed
32.
Li Z, Meng F, Li J, Wu T (2022) Donor-derived CD7 CAR-T therapy followed by allogeneic hematopoietic stem cell transplantation for acute T-Lymphocytic leukemia associated with hepatitis B: a case report. Front Immunol 13:931452PubMedPubMedCentral
33.
Jain P, Kantarjian H, Ravandi F, Thomas D, O’Brien S, Kadia T et al (2014) The combination of hyper-CVAD plus nelarabine as frontline therapy in adult T-cell acute lymphoblastic leukemia and T-lymphoblastic lymphoma: MD Anderson Cancer Center experience. Leukemia 28(4):973–975PubMed
34.
Burkhardt B, Reiter A, Landmann E, Lang P, Lassay L, Dickerhoff R et al (2009) Poor outcome for children and adolescents with progressive disease or relapse of lymphoblastic lymphoma: a report from the berlin-frankfurt-muenster group. J Clin Oncol 27(20):3363–3369PubMed
35.
Pui CH, Pei D, Coustan-Smith E, Jeha S, Cheng C, Bowman WP et al (2015) Clinical utility of sequential minimal residual disease measurements in the context of risk-based therapy in childhood acute lymphoblastic leukaemia: a prospective study. Lancet Oncol 16(4):465–474PubMedPubMedCentral
36.
Candoni A, Lazzarotto D, Ferrara F, Curti A, Lussana F, Papayannidis C et al (2020) Nelarabine as salvage therapy and bridge to allogeneic stem cell transplant in 118 adult patients with relapsed/refractory T-cell acute lymphoblastic leukemia/lymphoma. A CAMPUS ALL study. Am J Hematol 95(12):1466–72PubMed
37.
Caracciolo D, Mancuso A, Polerà N, Froio C, D’Aquino G, Riillo C et al (2023) The emerging scenario of immunotherapy for T-cell Acute Lymphoblastic Leukemia: advances, challenges and future perspectives. Exp Hematol Oncol 12(1):5PubMedPubMedCentral
38.
Maciocia PM, Wawrzyniecka PA, Philip B, Ricciardelli I, Akarca AU, Onuoha SC et al (2017) Targeting the T cell receptor β-chain constant region for immunotherapy of T cell malignancies. Nat Med 23(12):1416–1423PubMed
39.
Gomes-Silva D, Srinivasan M, Sharma S, Lee CM, Wagner DL, Davis TH et al (2017) CD7-edited T cells expressing a CD7-specific CAR for the therapy of T-cell malignancies. Blood 130(3):285–296PubMedPubMedCentral
40.
Png YT, Vinanica N, Kamiya T, Shimasaki N, Coustan-Smith E, Campana D (2017) Blockade of CD7 expression in T cells for effective chimeric antigen receptor targeting of T-cell malignancies. Blood Adv 1(25):2348–2360PubMedPubMedCentral
41.
Qi Y, Zhao M, Hu Y, Wang Y, Li P, Cao J et al (2022) Efficacy and safety of CD19-specific CAR T cell-based therapy in B-cell acute lymphoblastic leukemia patients with CNSL. Blood 139(23):3376–3386PubMedPubMedCentral
42.
Xie L, Ma L, Liu S, Chang L, Wen F (2021) Chimeric antigen receptor T cells targeting CD7 in a child with high-risk T-cell acute lymphoblastic leukemia. Int Immunopharmacol 96:107731PubMed
43.
Feng J, Xu H, Cinquina A, Wu Z, Chen Q, Zhang P et al (2021) Treatment of aggressive T cell lymphoblastic lymphoma/leukemia using Anti-CD5 CAR T cells. Stem Cell Rev Rep 17(2):652–661PubMedPubMedCentral
44.
Biondi M, Tettamanti S, Galimberti S, Cerina B, Tomasoni C, Piazza R et al (2023) Selective homing of CAR-CIK cells to the bone marrow niche enhances control of the acute myeloid leukemia burden. Blood 141(21):2587–2598PubMedPubMedCentral
45.
Mullanfiroze K, Lazareva A, Chu J, Williams L, Burridge S, Silva J et al (2022) CD34+-selected stem cell boost can safely improve cytopenias following CAR T-cell therapy. Blood Adv 6(16):4715–4718PubMedPubMedCentral
46.
Jost TR, Borga C, Radaelli E, Romagnani A, Perruzza L, Omodho L et al (2016) Role of CXCR4-mediated bone marrow colonization in CNS infiltration by T cell acute lymphoblastic leukemia. J Leukoc Biol 99(6):1077–1087PubMed
47.
Hong Z, Wei Z, Xie T, Fu L, Sun J, Zhou F et al (2021) Targeting chemokines for acute lymphoblastic leukemia therapy. J Hematol Oncol 14(1):48PubMedPubMedCentral
48.
Teicher BA, Fricker SP (2010) CXCL12 (SDF-1)/CXCR4 pathway in cancer. Clin Cancer Res 16(11):2927–2931PubMed
49.
Hu Y, Zhang M, Yang T, Mo Z, Wei G, Jing R et al (2024) Sequential CD7 CAR T-Cell Therapy and Allogeneic HSCT without GVHD Prophylaxis. N Engl J Med 390(16):1467–1480PubMed
50.
Zhang X, Yang J, Li J, Qiu L, Zhang J, Lu Y et al (2023) Analysis of 60 patients with relapsed or refractory T-cell acute lymphoblastic leukemia and T-cell lymphoblastic lymphoma treated with CD7-targeted chimeric antigen receptor-T cell therapy. Am J Hematol 98(12):1898–1908PubMed
Metadata
Title
Clinical outcomes and safety of CAR-T cells in treatment of T-Cell acute lymphoblastic leukemia/lymphoma
Authors
Jin-Feng Ma
Chun-Long Yan
Xu Jia
Hong-Jia Zhu
Jia-Wei Yan
Mei-Jing Liu
Dai-Yi Zhang
Shen-Hao Liu
Nan Xu
Hai-Guo Zhang
Ling Ye
Lei Yu
De-Pei Wu
Wen-Jie Gong
Hai-Ping Dai
Sheng-Li Xue
Publication date
18-12-2024
Publisher
Springer Berlin Heidelberg
Published in
Annals of Hematology / Issue 1/2025
Print ISSN: 0939-5555
Electronic ISSN: 1432-0584
DOI
https://doi.org/10.1007/s00277-024-06132-w

Other articles of this Issue 1/2025

A study of the relationship between circulating cytokines (interleukin-2 receptor and tumor necrosis factor receptor 2) and risk of B-cell non-hodgkin lymphoma

Whole exome sequencing analysis of a patient with myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions with ETV6::LYN fusion gene

A comprehensive analysis of the major specificities of anti-human T lymphocyte porcine immunoglobulin (p-ATG)

  • Open Access
  • Research

Cost-utility analysis of ropeginterferon alfa-2b to manage low-risk patients with polycythemia vera as compared to phlebotomy only in the Austrian healthcare system

Daratumumab, bortezomib, melphalan, and prednisone versus bortezomib, melphalan, and prednisone alone in transplant-ineligible Asian patients with newly diagnosed multiple myeloma: final analysis of the phase 3 OCTANS Study

Outcomes in patients with acute myeloid leukemia older than 70 years within the last 30 years, a single center experience

Elevate your expertise in aplastic anemia (Link opens in a new window)

Transform the way you care for your patients with aplastic anemia with our 3-module series using real-world case studies and expert insights. Discover why early diagnosis matters, explore the benefits and risks of current treatments, and develop tailored approaches for complex cases. 

Supported by:
  • Pfizer
Developed by: Springer Healthcare IME
Learn more

Keynote series | Spotlight on menopause

Menopause can have a significant impact on the body, with effects ranging beyond the endocrine and reproductive systems. Learn about the systemic effects of menopause, so you can help patients in your clinics through the transition.   

Prof. Martha Hickey
Dr. Claudia Barth
Dr. Samar El Khoudary
Developed by: Springer Medicine
Watch now
Video
Image Credits