Selecting the Optimal CAR-T for the Treatment of B-Cell Malignancies

Curr Hematol Malig Rep. 2021 Feb;16(1):32-39. doi: 10.1007/s11899-021-00615-7. Epub 2021 Feb 25.

Abstract

Purpose of review: Chimeric antigen receptor T-cell (CAR-T) therapy is a form of adoptive cellular therapy that has revolutionized the treatment landscape in hematologic malignancies, especially B-cell lymphomas. In this review, we will discuss some of the landmark data behind these therapies and then lay out our approach to utilizing this new therapy.

Recent findings: CD19-directed CAR-Ts are the most common type currently used in treatment of relapsed B-cell lymphoid neoplasms. There are currently three FDA-approved products: axicabtagene ciluecel and tisagenlecleucel for the treatment of relapsed/refractory large B-cell lymphoma and pediatric B-cell acute lymphocytic leukemia (tisagenlecleucel only) and brexucabtagene autoleucel for the treatment of relapsed/refractory mantle cell lymphoma. These therapies are associated with distinctive acute toxicities such as cytokine release syndrome and neurotoxicity and chronic toxicities such as cytopenias and hypogammaglobulinemia. CAR-T therapy provides significant potential in the treatment of relapsed B-cell lymphomas despite current limitations. Several novel CAR cell designs are currently being studied in clinical trials which include tandem CAR-Ts, allogeneic CAR-Ts, and CAR-NK cells.

Keywords: B-cell lymphoma; CAR-NK; Chimeric antigen receptor T-cell (CAR-T); Cytokine release syndrome; Novel CAR-T constructs.

Publication types

  • Review

MeSH terms

  • Animals
  • Antigens, CD19 / therapeutic use
  • B-Lymphocytes / immunology
  • B-Lymphocytes / pathology
  • Biological Products
  • Humans
  • Immunotherapy, Adoptive / methods*
  • Leukemia, B-Cell / immunology
  • Leukemia, B-Cell / pathology
  • Leukemia, B-Cell / therapy*
  • Lymphoma, B-Cell / immunology
  • Lymphoma, B-Cell / pathology
  • Lymphoma, B-Cell / therapy*
  • Receptors, Antigen, T-Cell / therapeutic use

Substances

  • Antigens, CD19
  • Biological Products
  • Receptors, Antigen, T-Cell
  • tisagenlecleucel
  • axicabtagene ciloleucel