Chimeric Antigen Receptor T-Cell (CAR T-Cell) Therapy for Primary and Secondary Central Nervous System Lymphoma: A Systematic Review of Literature

Clin Lymphoma Myeloma Leuk. 2023 Jan;23(1):15-21. doi: 10.1016/j.clml.2022.09.008. Epub 2022 Oct 7.


Relapsed/refractory central nervous system (CNS) lymphoma, whether primary or secondary, is associated with poor prognosis with currently available treatment modalities, including high-dose chemotherapy-autologous stem cell transplantation. The pivotal ZUMA-1 and JULIET trials that led to FDA approval of Axicabtagene ciloleucel and Tisagenlecleucel for relapsed refractory large cell lymphoma excluded patients with CNS involvement due to concerns of increased toxicity. However, TRANSCEND study for Lisocabtagene maraleucel in relapsed refractory large cell lymphoma allowed patients with CNS involvement and reported manageable CNS toxicities in these patients. In the real-world experience, chimeric antigen receptor T-cell (CAR T) therapy has been deemed safe and effective for these patients with poor prognosis. In this systematic review, we analyzed available literature to evaluate the role of CAR T-cell therapy in both primary and secondary CNS lymphoma using Embase, Cochrane, and PubMed databases. A total of 14 studies, including 8 retrospective analyses and 6 prospective studies/clinical trials, were included in the qualitative synthesis to study the safety and efficacy of CAR T. Based on our analysis, CAR T-cell therapy appears to be associated with reasonable efficacy and a manageable safety for primary and secondary CNS lymphoma.

Keywords: Axicabtagene ciloleucel; Chimeric antigen receptor T-cell therapy; Lisocabtagene maraleucel; Primary CNS lymphoma; Relapsed and refractory; Secondary CNS lymphoma; Tisagenlecleucel.

Publication types

  • Systematic Review
  • Review

MeSH terms

  • Antigens, CD19
  • Central Nervous System / pathology
  • Central Nervous System Neoplasms* / drug therapy
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Immunotherapy, Adoptive / adverse effects
  • Lymphoma* / drug therapy
  • Lymphoma, Large B-Cell, Diffuse* / pathology
  • Lymphoma, Non-Hodgkin* / drug therapy
  • Neoplasms, Second Primary*
  • Prospective Studies
  • Receptors, Antigen, T-Cell
  • Receptors, Chimeric Antigen*
  • Retrospective Studies
  • T-Lymphocytes
  • Transplantation, Autologous


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