How I treat refractory/relapsed diffuse large B-cell lymphomas with CD19-directed chimeric antigen receptor T cells

Br J Haematol. 2023 May;201(3):396-410. doi: 10.1111/bjh.18724. Epub 2023 Mar 14.

Abstract

Chimeric antigen receptor (CAR) T cells targeting CD19 represent a promising salvage immunotherapy for relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL), offering ~40% of long-term responses. In everyday clinical practice, haematologists involved in CAR T cell treatment of patients with R/R DLBCL have to deal with diagnostically complex cases and difficult therapeutic choices. The availability of novel immunotherapeutic agents for R/R DLBCL and recent advances in understanding CAR T-cell failure mechanisms demand a rational approach to identify the best choice for bridging therapy and managing post-CAR T-cell therapy relapses. Moreover, positron emission tomography/computerised tomography may result in false-positive interpretation, highlighting the importance of post-treatment biopsy. In this review, we discuss all above issues, presenting four instructive cases, with the aim to provide criteria and new perspectives for CAR T-cell treatment of DLBCL.

Keywords: CD19; Chimeric antigen receptor (CAR) T cells; cytokine release syndrome (CRS); immune effector cell-associated neurotoxicity syndrome (ICANS); immunohistochemistry; lymphoma; monoclonal antibodies.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD19
  • Humans
  • Immunotherapy, Adoptive / methods
  • Lymphoma, Large B-Cell, Diffuse* / drug therapy
  • Neoplasm Recurrence, Local / etiology
  • Receptors, Antigen, T-Cell / therapeutic use
  • Receptors, Chimeric Antigen* / therapeutic use
  • T-Lymphocytes

Substances

  • Receptors, Chimeric Antigen
  • Receptors, Antigen, T-Cell
  • Antigens, CD19