Early granulocyte colony stimulating factor administration increases the risk of cytokine release syndrome in acute lymphoblastic leukemia patients receiving anti-CD19 chimeric antigen receptor T-cell therapy

Hematol Oncol. 2023 Dec;41(5):933-941. doi: 10.1002/hon.3188. Epub 2023 May 31.

Abstract

Cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS) and neutropenia are common toxicities associated with chimeric antigen receptor T (CAR-T) cell therapy. The role of granulocyte colony stimulating factor (G-CSF) in CAR-T-cell-treated patients remains unclear. To explore the efficacy and safety of early G-CSF administration in patients with relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL) who were receiving autologous anti-CD19 CAR-T cells, we retrospectively collected and summarized clinical data to compare patients receiving G-CSF within 14 days (early G-CSF group) to patients receiving later or no G-CSF (control group) after their CART infusion. The results showed that there was no significant difference in the incidence and duration of neutropenia between the early G-CSF group and the control group (77% vs. 63%, p = 0.65; 8 vs. 4 days, p = 0.37, respectively). However, the incidence and duration of CRS were significantly higher in the early G-CSF group than in the control group (81% vs. 38%, p = 0.03; 3 vs. 0 days, p = 0.004, respectively). Moreover, early G-CSF application had no significant effect on the expansion and efficacy of CAR-T cells. In conclusion, our study suggested that early G-CSF administration did not reduce the incidence and duration of neutropenia but rather increased the incidence and duration of CRS.

Keywords: ALL; CAR-T; CRS; G-CSF; neutropenia.

MeSH terms

  • Antigens, CD19
  • Cell- and Tissue-Based Therapy / adverse effects
  • Cytokine Release Syndrome / etiology
  • Granulocyte Colony-Stimulating Factor / therapeutic use
  • Humans
  • Neutropenia*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma* / drug therapy
  • Receptors, Chimeric Antigen* / therapeutic use
  • Retrospective Studies

Substances

  • Receptors, Chimeric Antigen
  • Granulocyte Colony-Stimulating Factor
  • Antigens, CD19