Correlation of IL-6 secretion and hyponatremia with the use of CD19+ chimeric antigen receptor T-cells

Clin Nephrol. 2020 Jan;93(1):42-46. doi: 10.5414/CN109872.

Abstract

Background: Various studies have demonstrated that interleukin-6 (IL-6) activates the central magnocellular arginine vasopressin (AVP)-secreting neurons in the brain to produce non-osmotic, non-volume-mediated increases in AVP. The most common toxicity of CD19+ chimeric antigen receptor (CAR) T-cells is cytokine release syndrome, which is related to increased levels of IL-6. This study will evaluate the correlation of IL-6 levels with hyponatremia in patients receiving CD19+ CAR T-cells.

Materials and methods: This is a single-center retrospective analysis of adult patients who received CD19+ CAR T-cells for the treatment of relapsed/refractory acute lymphoblastic leukemia (ALL).

Results: Hyponatremia, defined as a serum sodium (Na) ≤ 135 mEq/L, occurred in 31 (61%) patients. A change in Na > 7 mEq occurred in 32 (63%) patients, and the median lowest Na was 133 mEq/L (interquartile range (IQR): 131 - 136)). There was an inverse linear relationship between IL-6 levels and lowest Na (p = 0.001). Overall, per 10-fold increase in IL-6, Na decreased by an average of 2.68 mEq/L.

Conclusion: Hyponatremia is common in patients who received CD19+ CAR T-cells. There is an inverse linear relationship between IL-6 levels and nadir Na (p = 0.001). Further studies will be needed to confirm a causative relationship between IL-6 levels and hyponatremia following CD19+ CAR T-cell infusion.

MeSH terms

  • Adult
  • Aged
  • Antigens, CD19 / metabolism
  • Female
  • Humans
  • Hyponatremia / blood*
  • Hyponatremia / etiology*
  • Immunotherapy, Adoptive / adverse effects*
  • Interleukin-6 / blood*
  • Male
  • Middle Aged
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / therapy
  • Receptors, Chimeric Antigen
  • Retrospective Studies
  • Sodium / blood*
  • T-Lymphocytes / metabolism
  • Young Adult

Substances

  • Antigens, CD19
  • Interleukin-6
  • Receptors, Chimeric Antigen
  • Sodium