Toxicities and Response Rates of Secondary CNS Lymphoma After Adoptive Immunotherapy With CD19-Directed Chimeric Antigen Receptor T Cells

Neurology. 2022 May 24;98(21):884-889. doi: 10.1212/WNL.0000000000200608. Epub 2022 Mar 29.

Abstract

Background and objectives: Secondary CNS involvement in systemic B-cell lymphoma (SCNSL) is difficult to treat and displays dismal clinical outcomes. Chimeric antigen receptor (CAR) T cells emerged as a powerful treatment for systemic lymphoma. We aimed to evaluate whether CAR T cells also represent a safe and effective therapy for SCNSL.

Methods: We retrospectively searched our institutional database for patients with SCNSL treated with CD19-directed CAR T cells.

Results: We identified 10 cases, including 7 patients with intraparenchymal lesions and 3 patients with leptomeningeal disease. CNS staging at 1 month after CAR T-cell transfusion showed disease response (stable disease, partial response, and complete response) in 7 patients (70%), including 2 cases of long-lasting complete response (20%). One patient developed pseudoprogression, which resolved under steroids. Response of CNS disease was associated with systemic 1-month response. With a median follow-up of 6 months, median overall and systemic progression-free survival was 7 and 3 months, respectively. Neurotoxic symptoms occurred in 6 patients, with 3 patients developing severe neurotoxicity (American Society for Transplantation and Cellular Therapy grade ≥3).

Discussion: CAR T cells induce considerable antitumor effects in SCNSL, and CNS response reflects systemic response. Neurotoxicity appears similar to previous reports on patients with lymphoma without CNS involvement. CAR T cells may therefore represent an effective and safe therapy for SCNSL.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD19
  • Central Nervous System Neoplasms* / therapy
  • Humans
  • Immunotherapy, Adoptive / adverse effects
  • Lymphoma* / therapy
  • Lymphoma, B-Cell* / therapy
  • Receptors, Antigen, T-Cell
  • Receptors, Chimeric Antigen* / therapeutic use
  • Retrospective Studies
  • T-Lymphocytes

Substances

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