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Hypophosphatemia and pre-infusion thrombocytopenia as biomarkers for CRS and ICANS after CAR T therapy

Bone Marrow Transplantation volume 58, pages 1267–1269 (2023)Cite this article

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The treatment paradigm of B cell malignancies has been profoundly altered by CAR T-cell therapy. Adverse effects of CAR T include cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Several predictive biomarkers have been strongly associated with the development of CRS and/or ICANS following CAR T infusion including increased levels of IL-6, interferon-γ, ANG-2, VWF, IL-2, and IL-10 [1,2,3]. Treatment models using these biomarkers have been proposed to predict CRS and/or ICANS with moderate specificity and sensitivity. However, measuring cytokines can often take multiple days depending on the institution and the laboratory. Review of our CAR T single institution experience revealed that monitoring common same day laboratory findings such as pre-infusion platelet count and serial phosphate levels hold promise in early identification of patients developing CRS and/or ICANS.

A total of 35 patients (19 male and 16 female) with a median age of 68 years and ranging from 38 to 80 years old treated with CAR T-cells for B-cell malignancies at Banner University Medical Center/University of Arizona Cancer Center were retrospectively chart reviewed. Patient’s age, gender, type of infusion product and type of malignancy were all recorded. Diagnosis of CRS and ICANS with associated grade were recorded for each patient. Phosphate levels were recorded up to 10 days prior to CAR T infusion and up to 25 days post infusion, and the presence of hypophosphatemia was defined as < 2.4 mg/dL per institutional normal values. Platelet counts were recorded at the day of infusion, and the presence of thrombocytopenia was defined as a pre-infusion platelet count of <130 K/uL per institutional normal values. LDH and ferritin levels were recorded as the peak level up to 25 days after infusion. LDH elevation and ferritin elevation were defined as >225 IU/L and >506 ng/mL respectively per institutional normal levels.

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Fig. 1: Each biomarker was investigated up to 25 days after infusion looking for either nadir or peak levels.

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Authors and Affiliations

  1. Department of Medicine, University of Arizona, Tucson, AZ, USA

    Kenneth Barker & Muhammad Husnain

  2. University of Arizona Cancer Center, Tucson, AZ, USA

    Shannon Koza, Emmanuel Katsanis & Muhammad Husnain

  3. Departments of Immunobiology, Medicine, and Pathology, University of Arizona, Tucson, AZ, USA

    Emmanuel Katsanis

  4. Department of Pediatrics, University of Arizona, Tucson, AZ, USA

    Emmanuel Katsanis

Authors
  1. Kenneth Barker
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  2. Shannon Koza
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  3. Emmanuel Katsanis
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  4. Muhammad Husnain
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Contributions

KB collected and analyzed the data and wrote the manuscript. SK contributed the original idea for the project. MH and EK contributed to project design/oversight and editing of the manuscript. All authors revised and approved the final manuscript.

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Correspondence to Kenneth Barker.

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Barker, K., Koza, S., Katsanis, E. et al. Hypophosphatemia and pre-infusion thrombocytopenia as biomarkers for CRS and ICANS after CAR T therapy. Bone Marrow Transplant 58, 1267–1269 (2023). https://doi.org/10.1038/s41409-023-02083-4

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