CD19 CAR-T cell therapy for relapsed or refractory diffuse large B cell lymphoma: Why does it fail?

Semin Hematol. 2023 Nov;60(5):329-337. doi: 10.1053/j.seminhematol.2023.11.007. Epub 2023 Dec 5.

Abstract

Chimeric antigen receptor T (CAR-T) cell therapy is an effective treatment for relapsed or refractory diffuse large B cell lymphoma (DLBCL) with 3 CD19 targeting products now FDA-approved for this indication. However, up to 60% of patients ultimately progress or relapse following CAR-T cell therapy. Mechanisms of resistance to CAR-T cell therapy in patients with DLBCL are likely multifactorial and have yet to be fully elucidated. Determining patient, tumor and therapy-related factors that may predict an individual's response to CAR-T cell therapy requires ongoing analysis of data from clinical trials and real-world experience in this population. In this review we will discuss the factors identified to-date that may contribute to failure of CAR-T cell therapy in achieving durable remissions in patients with DLBCL.

Keywords: CAR-T cell therapy; CAR-T failure, lymphoma; DLBCL.

Publication types

  • Review

MeSH terms

  • Antigens, CD19 / therapeutic use
  • Cell- and Tissue-Based Therapy
  • Humans
  • Immunotherapy, Adoptive
  • Lymphoma, Large B-Cell, Diffuse* / drug therapy
  • Lymphoma, Large B-Cell, Diffuse* / pathology
  • Neoplasm Recurrence, Local / etiology
  • Receptors, Antigen, T-Cell / therapeutic use
  • Receptors, Chimeric Antigen*

Substances

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