Effect of early granulocyte-colony-stimulating factor administration in the prevention of febrile neutropenia and impact on toxicity and efficacy of anti-CD19 CAR-T in patients with relapsed/refractory B-cell lymphoma

Bone Marrow Transplant. 2022 Mar;57(3):431-439. doi: 10.1038/s41409-021-01526-0. Epub 2022 Jan 30.

Abstract

Chimeric Antigen Receptor T cells (CAR-T) are an outbreaking treatment option for relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL). Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) are the most common specific toxicities, while severe neutropenia and infections are often observed as well. From March 2020, early G-CSF prophylaxis at day (D) two post-infusion was systematically proposed. We then compared patients treated before that date who did not receive G-CSF or who received late (after D5) G-CSF as control group. Patients administered with early G-CSF had similar duration of grade 4 neutropenia but significantly decreased incidence of febrile neutropenia (58% versus 81%, p = 0.018). Similar rate of toxicities was observed, including overall and grade 3-4 CRS (p = 0.93 and p = 0.28, respectively), and overall and grade 3-4 ICANS (p = 0.62 and p = 0.88, respectively). We observed no difference in the quality of CAR T-cells expansion (p = 0.79, %Cmax), nor in response rate (best ORR, 57.6% vs 61.8%, p = 0.93), nor survival even in a group of patients adjusted by a propensity score. In conclusion, early G-CSF administration was safe and effective in reducing febrile neutropenia without impact on toxicities nor on anti-lymphoma activity of CAR-T.

MeSH terms

  • Antigens, CD19
  • Febrile Neutropenia* / etiology
  • Febrile Neutropenia* / prevention & control
  • Granulocyte Colony-Stimulating Factor / therapeutic use
  • Granulocytes
  • Humans
  • Immunotherapy, Adoptive / adverse effects
  • Lymphoma, Large B-Cell, Diffuse* / drug therapy
  • Receptors, Chimeric Antigen*

Substances

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