Associations of granulocyte colony-stimulating factor with toxicities and efficacy of chimeric antigen receptor T-cell therapy in relapsed or refractory B-cell acute lymphoblastic leukemia

Cancer Immunol Immunother. 2024 Apr 17;73(6):104. doi: 10.1007/s00262-024-03661-1.

Abstract

Few studies have reported the associations of granulocyte colony-stimulating factor (G-CSF) with cytokine release syndrome (CRS), neurotoxic events (NEs) and efficacy after chimeric antigen receptor (CAR) T-cell therapy for relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). We present a retrospective study of 67 patients with R/R B-ALL who received anti-CD19 CAR T-cell therapy, 41 (61.2%) patients received G-CSF (G-CSF group), while 26 (38.8%) did not (non-G-CSF group). Patients had similar duration of grade 3-4 neutropenia between the two groups. The incidences of CRS and NEs were higher in G-CSF group, while no differences in severity were found. Further stratified analysis showed that the incidence and severity of CRS were not associated with G-CSF administration in patients with low bone marrow (BM) tumor burden. None of the patients with low BM tumor burden developed NEs. However, there was a significant increase in the incidence of CRS after G-CSF administration in patients with high BM tumor burden. The duration of CRS in patients who used G-CSF was longer. There were no significant differences in response rates at 1 and 3 months after CAR T-cell infusion, as well as overall survival (OS) between the two groups. In conclusion, our results showed that G-CSF administration was not associated with the incidence or severity of CRS in patients with low BM tumor burden, but the incidence of CRS was higher after G-CSF administration in patients with high BM tumor burden. The duration of CRS was prolonged in G-CSF group. G-CSF administration was not associated with the efficacy of CAR T-cell therapy.

Keywords: B-cell acute lymphoblastic leukemia; Chimeric antigen receptor T-cell therapy; Cytokine release syndrome; Efficacy; Granulocyte colony-stimulating factor; Neurotoxic events.

MeSH terms

  • Cell- and Tissue-Based Therapy
  • Cytokine Release Syndrome
  • Granulocyte Colony-Stimulating Factor / therapeutic use
  • Humans
  • Immunotherapy, Adoptive / adverse effects
  • Neurotoxicity Syndromes*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma* / therapy
  • Receptors, Chimeric Antigen*
  • Retrospective Studies

Substances

  • Receptors, Chimeric Antigen
  • Granulocyte Colony-Stimulating Factor