☆ 4.3 Review

Current status of CAR-T cell therapy for pediatric hematologic malignancies

INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY (2023)

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Article Oncology

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

Tianyi Wang et al.

Summary: This study aimed to evaluate the safety and efficacy of coadministration of CD19- and CD22-chimeric antigen receptor (CAR) T cells in patients with refractory or relapsed B-acute lymphoblastic leukemia. The results showed that 99.0% of patients with refractory leukemia or hematologic relapse achieved complete remission, and all patients were negative for minimal residual disease. Consolidative transplantation and persistent B-cell aplasia at 6 months were associated with favorable outcomes. However, cytokine release syndrome and CAR T-cell neurotoxicity occurred in a minority of patients.

JOURNAL OF CLINICAL ONCOLOGY (2023)

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Article Oncology

Three-Year Update of Tisagenlecleucel in Pediatric and Young Adult Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia in the ELIANA Trial

Theodore W. Laetsch et al.

Summary: Clinical trials often have multiple endpoints with different maturity times. Clinical Trial Updates provide an opportunity to publish additional results beyond the initial report based on the primary endpoint. This update on the ELIANA trial demonstrates the long-term efficacy, safety, and quality of life improvements in pediatric and young adult patients with R/R B-ALL treated with tisagenlecleucel.

JOURNAL OF CLINICAL ONCOLOGY (2023)

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Article Oncology

Blinatumomab Nonresponse and High-Disease Burden Are Associated With Inferior Outcomes After CD19-CAR for B-ALL

Regina M. Myers et al.

Summary: This retrospective study investigates the impact of CD19-CAR therapy on relapsed or refractory ALL patients, revealing that nonresponse to blinatumomab and high disease burden are associated with worse survival outcomes.

JOURNAL OF CLINICAL ONCOLOGY (2022)

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Article Hematology

Parameters of long-term response with CD28-based CD19 chimaeric antigen receptor-modified T cells in children and young adults with B-acute lymphoblastic leukaemia

Elad Jacoby et al.

Summary: This study reported the long-term outcome of 37 children and young adults treated with autologous CD19 CAR-T cells, with a complete remission rate of 86% and 41% three-year EFS. Prelymphodepletion disease burden and molecular MRD negativity following CAR-T cells are predictors of long-term outcome.

BRITISH JOURNAL OF HAEMATOLOGY (2022)

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Article Hematology

Hematopoietic Cell Transplantation after CD19 Chimeric Antigen Receptor T Cell-Induced Acute Lymphoblastic Leukemia Remission Confers a Leukemia-Free Survival Advantage

Corinne Summers et al.

Summary: This study evaluated the effect of consolidative HCT on leukemia-free survival (LFS) in pediatric and young adult subjects following CD19 CART cell induced remission. The results showed that consolidative HCT improved LFS specifically in subjects who had no prior history of HCT and those with short functional CART cell persistence.

TRANSPLANTATION AND CELLULAR THERAPY (2022)

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Article Oncology

Next-Generation Sequencing of Minimal Residual Disease for Predicting Relapse after Tisagenlecleucel in Children and Young Adults with Acute Lymphoblastic Leukemia

Michael A. Pulsipher et al.

Summary: We assessed minimal residual disease (MRD) detection and B-cell aplasia after tisagenlecleucel therapy for acute lymphoblastic leukemia (ALL) to identify predictive biomarkers for relapse. The results showed that BMNGS-MRD 0 and B-cell recovery were independently associated with relapse, and detectable BMNGS-MRD reliably predicted the risk.

BLOOD CANCER DISCOVERY (2022)

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Article Oncology

CAR T-cells that target acute B-lineage leukemia irrespective of CD19 expression

Kristen Fousek et al.

Summary: Chimeric antigen receptor (CAR) T-cells targeting CD19 have shown effectiveness in treating B-lineage acute lymphoblastic leukemia (BL-ALL), but a significant number of patients relapse with CD19(-) disease. This study demonstrates that creating a CD19/20/22-targeting CAR T-cell can effectively target CD19(-) escape leukemia cells, forming dense immune synapses at the subcellular level.

LEUKEMIA (2021)

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Article Oncology

Risk-Adapted Preemptive Tocilizumab to Prevent Severe Cytokine Release Syndrome After CTL019 for Pediatric B-Cell Acute Lymphoblastic Leukemia: A Prospective Clinical Trial

Stephan Kadauke et al.

Summary: The study evaluated the effectiveness of risk-adapted preemptive tocilizumab treatment in preventing severe cytokine release syndrome after CTL019 therapy, showing a decrease in the expected incidence of grade 4 CRS without impacting the antitumor efficacy of CTL019.

JOURNAL OF CLINICAL ONCOLOGY (2021)

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Article Oncology

Long-Term Follow-Up of CD19-CAR T-Cell Therapy in Children and Young Adults With B-ALL

Nirali N. Shah et al.

Summary: CD19-CAR T-cell therapy shows high response rates in CAYAs with B-ALL, but high relapse rates. Sequential therapy with CD19.28 zeta-CAR T cells followed by alloHSCT can achieve durable disease control in a sizable fraction of patients.

JOURNAL OF CLINICAL ONCOLOGY (2021)

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Article Oncology

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

Marie-Emilie Dourthe et al.

Summary: Tisagenlecleucel therapy has shown promising efficacy in relapsed/refractory BCP-ALL patients, with a high complete remission rate at D28. However, factors such as prior therapy and disease burden can impact the risk of relapse and overall survival. Detectable MRD at D28 and loss of BCA may define patients at high risk of relapse, requiring additional interventions.

LEUKEMIA (2021)

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Review Oncology

Consolidative Hematopoietic Stem Cell Transplantation After CD19 CAR-T Cell Therapy for Acute Lymphoblastic Leukemia: A Systematic Review and Meta-analysis

Xinjie Xu et al.

Summary: This study systematically evaluated and compared the efficacy and safety of consolidative HSCT after CD19 CAR-T therapy with non-HSCT in the treatment of ALL. The results showed that consolidative HSCT after CD19 CAR-T therapy could prolong OS and LFS and reduce the risk of relapse, with acceptable incidence rates for adverse events. More high-quality randomized controlled trials are needed to further determine the efficacy of HSCT.

FRONTIERS IN ONCOLOGY (2021)

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Article Oncology

Optimizing Chimeric Antigen Receptor T-Cell Therapy for Adults With Acute Lymphoblastic Leukemia

Noelle Frey et al.

JOURNAL OF CLINICAL ONCOLOGY (2020)

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Article Oncology

Bispecific CAR-T cells targeting both CD19 and CD22 for therapy of adults with relapsed or refractory B cell acute lymphoblastic leukemia

Hanren Dai et al.

JOURNAL OF HEMATOLOGY & ONCOLOGY (2020)

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Review Biotechnology & Applied Microbiology

Sequential Infusion of Anti-CD22 and Anti-CD19 Chimeric Antigen Receptor T Cells for a Pediatric Ph-Like B-ALL Patient That Relapsed After CART-Cell and Haplo-HSCT Therapy: A Case Report and Review of Literature

Jingsheng Hua et al.

ONCOTARGETS AND THERAPY (2020)

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Article Hematology

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

Xian Zhang et al.

BLOOD ADVANCES (2020)

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Article Hematology

Real-world evidence of tisagenlecleucel for pediatric acute lymphoblastic leukemia and non-Hodgkin lymphoma

Marcelo C. Pasquini et al.

BLOOD ADVANCES (2020)

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Article Biophysics

The role of allogeneic HSCT after CAR T cells for acute lymphoblastic leukemia

Elad Jacoby

BONE MARROW TRANSPLANTATION (2019)

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Article Hematology

Toxicity and response after CD19-specific CAR T-cell therapy in pediatric/young adult relapsed/refractory B-ALL

Kevin J. Curran et al.

BLOOD (2019)

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Article Hematology

ASTCT Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with Immune Effector Cells

Daniel W. Lee et al.

BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION (2019)

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Article Hematology

Preemptive mitigation of CD19 CAR T-cell cytokine release syndrome without attenuation of antileukemic efficacy

Rebecca A. Gardner et al.

BLOOD (2019)

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Article Biochemistry & Molecular Biology

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

Terry J. Fry et al.

NATURE MEDICINE (2018)

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Review Biochemistry & Molecular Biology

Incorporation of Immune Checkpoint Blockade into Chimeric Antigen Receptor T Cells (CAR-Ts): Combination or Built-In CAR-T

Dok Hyun Yoon et al.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2018)

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Article Medicine, General & Internal

Tisagenlecleucel in Children and Young Adults with B-Cell Lymphoblastic Leukemia

S. L. Maude et al.

NEW ENGLAND JOURNAL OF MEDICINE (2018)

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Article Biochemistry & Molecular Biology

Genetic mechanisms of target antigen loss in CAR19 therapy of acute lymphoblastic leukemia

Elena J. Orlando et al.

NATURE MEDICINE (2018)

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Article Oncology

Childhood, adolescent and young adult cancer incidence in Japan in 2009-2011

Kota Katanoda et al.

JAPANESE JOURNAL OF CLINICAL ONCOLOGY (2017)

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Article Biotechnology & Applied Microbiology

Integration of a CD19 CAR into the. TCR Alpha Chain Locus Streamlines Production of Allogeneic Gene-Edited CAR T Cells

Daniel T. MacLeod et al.

MOLECULAR THERAPY (2017)

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Review Pharmacology & Pharmacy

Development of CAR T cells designed to improve antitumor efficacy and safety

Janneke E. Jaspers et al.

PHARMACOLOGY & THERAPEUTICS (2017)

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Article Cell Biology

Molecular remission of infant B-ALL after infusion of universal TALEN gene-edited CAR T cells

Waseem Qasim et al.

SCIENCE TRANSLATIONAL MEDICINE (2017)

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Article Oncology

CD19-negative relapse of pediatric B-cell precursor acute lymphoblastic leukemia following blinatumomab treatment

E. Mejstrikova et al.

BLOOD CANCER JOURNAL (2017)

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Article Hematology

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

Rebecca A. Gardner et al.

BLOOD (2017)

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Article Biochemistry & Molecular Biology

Catch me if you can: Leukemia Escape after CD19-Directed T Cell Immunotherapies

Marco Ruella et al.

COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL (2016)

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Article Cell & Tissue Engineering

Low-cost generation of Good Manufacturing Practice-grade CD19-specific chimeric antigen receptor-expressing T cells using piggyBac gene transfer and patient-derived materials

Saumya Ravianayake et al.

CYTOTHERAPY (2015)

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Article Oncology

Convergence of Acquired Mutations and Alternative Splicing of CD19 Enables Resistance to CART-19 Immunotherapy

Elena Sotillo et al.

CANCER DISCOVERY (2015)

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Article Cell & Tissue Engineering

Anti-leukemic potency of piggyBac-mediated CD 19-specific T cells against refractory Philadelphia chromosome-positive acute lymphoblastic leukemia

Shoji Saito et al.

CYTOTHERAPY (2014)

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Article Medicine, General & Internal

Chimeric Antigen Receptor T Cells for Sustained Remissions in Leukemia

Shannon L. Maude et al.

NEW ENGLAND JOURNAL OF MEDICINE (2014)

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Article Medicine, General & Internal

Chimeric Antigen Receptor-Modified T Cells for Acute Lymphoid Leukemia

Stephan A. Grupp et al.

NEW ENGLAND JOURNAL OF MEDICINE (2013)

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Article Medicine, General & Internal

Chimeric Antigen Receptor-Modified T Cells in Chronic Lymphoid Leukemia

David L. Porter et al.

NEW ENGLAND JOURNAL OF MEDICINE (2011)

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Article Oncology

Redirecting specificity of T-cell Populations for CD19 using the Sleeping beauty system

Harjeet Singh et al.

CANCER RESEARCH (2008)

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Article Oncology

A phase I study on adoptive immunotherapy using gene-modified T cells for ovarian cancer

Michael H. Kershaw et al.

CLINICAL CANCER RESEARCH (2006)

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