Plasma Exchange Can Be an Alternative Therapeutic Modality for Severe Cytokine Release Syndrome after Chimeric Antigen Receptor-T Cell Infusion: A Case Report

Clin Cancer Res. 2019 Jan 1;25(1):29-34. doi: 10.1158/1078-0432.CCR-18-1379. Epub 2018 Oct 15.

Abstract

Background: Tumor immunotherapy with chimeric antigen receptor-T cells (CAR-T) is a promising new treatment for B-cell malignancies and has produced exciting results. However, cytokine release syndrome (CRS) is the most significant toxicity associated with this treatment and can be life-threatening.

Case presentation: A 23-year-old male patient had been diagnosed with relapsed and refractory B-cell acute lymphocytic leukemia. The patient was recruited into our CAR-T clinical trial, and 1 × 106/kg of engineered anti-CD19 CAR-T cells was administered. After infusion of CAR-T cells (day 0), the patient underwent a typical CRS reaction, with increases in fever, muscle soreness, and inflammatory cytokines. He was treated with antiallergic and antipyretic drugs, glucocorticoids, and tocilizumab (4 mg/kg, days 3 and 5). However, CRS was not under control, and his condition rapidly deteriorated. He was transferred to the intensive care unit, where dexamethasone 10 mg q6h was administered, and plasma exchange was performed, with 3,000 mL of plasma replaced by fresh frozen plasma per day for 3 consecutive days. His symptoms gradually improved, and the CRS-related symptoms were relieved. Additionally, a bone marrow smear showed no lymphoblast cells, and minimal residual disease was negative on day 28. The patient was eventually discharged in a normal condition.

Conclusions: CRS is caused by an exaggerated systemic immune response, potentially resulting in organ damage that can be fatal. Although therapeutic plasma exchange is not included in CRS management guidelines, this case shows that plasma exchange is feasible in at least some patients with severe CRS.

Publication types

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

MeSH terms

  • Adult
  • Antigens, CD19 / blood
  • Antigens, CD19 / therapeutic use
  • Cytokine Release Syndrome / blood
  • Cytokine Release Syndrome / pathology
  • Cytokine Release Syndrome / therapy*
  • Cytokines / immunology
  • Glucocorticoids / therapeutic use
  • Humans
  • Immunotherapy, Adoptive / methods
  • Lymphoma, B-Cell / blood
  • Lymphoma, B-Cell / pathology
  • Lymphoma, B-Cell / therapy*
  • Male
  • Plasma Exchange / methods
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / blood
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / therapy*
  • Receptors, Antigen, T-Cell / therapeutic use*
  • Receptors, Chimeric Antigen / immunology
  • Receptors, Chimeric Antigen / therapeutic use

Substances

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