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CAR-T Cell Therapy for Acute Lymphoblastic Leukemia: Transforming the Treatment of Relapsed and Refractory Disease

  • Acute Lymphocytic Leukemias (K Ballen and M Keng, Section Editors)
  • Published:
Current Hematologic Malignancy Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Genetically engineered T cells expressing a chimeric antigen receptor (CAR-T) targeting specific antigens present on acute lymphoblastic leukemia (ALL) blasts have generated promising results in children and adults with relapsed and refractory disease. We review the current evidence for CAR-T cell therapy in ALL, associated toxicities, and efforts to improve durable response to therapy.

Recent Findings

CD19-directed CAR-T cells have recently been approved by the FDA for use in children and young adults with ALL and in adults with diffuse large B cell lymphoma (DLBCL) in the relapsed/refractory setting. CD22-directed CAR-T cells have shown efficacy against leukemia as well in a recent clinical trial, representing the first alternative CAR target to approach comparable efficacy to CD19 CAR-T cells. Standardization of toxicity grading and management, strategies to combat significant relapse rates after CAR-T therapy, and applicability of CAR-T cells to treat central nervous system (CNS) disease remain challenges in the field and represent priorities for continued research.

Summary

CAR-T cells are a feasible, effective, and rapidly evolving therapy for patients with relapsed and refractory B cell malignancies.

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Funding

Dr. Lee receives research funding from a St. Baldrick’s Foundation Scholar Award.

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Authors and Affiliations

  1. Division of Pediatric Hematology/Oncology, Department of Pediatrics, University of Virginia, Charlottesville, VA, USA

    Katherine C. Pehlivan

  2. Department of Pediatrics, University of Virginia, Charlottesville, VA, USA

    Brynn B. Duncan

  3. Division of Pediatric Hematology/Oncology, Department of Pediatrics, Department of Internal Medicine, University of Virginia, PO Box 800386, Charlottesville, VA, 22908, USA

    Daniel W. Lee

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  1. Katherine C. Pehlivan
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Correspondence to Daniel W. Lee.

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Conflict of Interest

Daniel W. Lee is a principal investigator on ZUMA4 CD19 CAR T cell Phase I/II study in pediatric ALL at the University of Virginia and receives research funding from a St. Baldrick’s Foundation Scholar Award.

Katherine C. Pehlivan and Brynn B. Duncan declare that they have no conflict of interest.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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This article is part of the Topical Collection on Acute Lymphocytic Leukemias

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Pehlivan, K.C., Duncan, B.B. & Lee, D.W. CAR-T Cell Therapy for Acute Lymphoblastic Leukemia: Transforming the Treatment of Relapsed and Refractory Disease. Curr Hematol Malig Rep 13, 396–406 (2018). https://doi.org/10.1007/s11899-018-0470-x

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