Low blood phosphate levels may be linked to neurological side effects from CAR T-cell therapy (Watch your phosphate level)

Medical Xpress / American Association for Cancer Research / Cancer Immunology Research ^ | Oct. 19, 2022 | Jack Pengfei Tang et al

[ConservativeMind]

Incidence and severity of neurological side effects from chimeric antigen receptor (CAR) T-cell therapy were higher in patients who had hypophosphatemia (low blood phosphate levels).

Neurological toxicity associated with CAR T-cell therapy, known as immune effector cell-associated neurotoxicity syndrome (ICANS), affects approximately 50% of recipients. Symptoms include confusion, delirium, aphasia, impaired motor skills, and somnolence. In severe cases, life-threatening events, including seizures and coma, can occur.

The researchers co-cultured lymphoma cells expressing the CD19 antigen with CD19-targeted CAR T cells and found that lymphoma cell killing was associated with reduced phosphate concentrations in the culture media. Furthermore, CAR T cells co-cultured with lymphoma cells consumed significantly more phosphate than when cultured alone.

The increased phosphate consumption of CAR T cells correlated with their activation following CD19 antigen recognition—as shown by increased cytokine release—and with elevated phosphate-dependent metabolic activity. These findings indicate that CAR T cell–mediated cell killing results in heightened metabolic demand that could drive hypophosphatemia in patients.

In this cohort, 30% of the patients developed ICANS, and approximately 60% had hypophosphatemia (defined as serum phosphate concentrations lower than 2mg/dL). Although the serum levels of potassium and magnesium were also low in 52% and 72% of the patients, respectively, only low phosphate was significantly associated with ICANS, with most patients who developed ICANS (91%) also displaying hypophosphatemia. In addition, the patients had the lowest phosphate concentrations five days post-CAR T cell infusion, which coincided with the median time to onset of ICANS.

The authors did not observe a significant difference in ICANS severity between patients who had hypophosphatemia and those who did not. However, patients with low phosphate levels experienced significantly longer duration of ICANS than patients with phosphate levels within normal range.

[ConservativeMind]

Low phosphate appears to be a concern only with the length of the severe symptoms, not with the severity. Unfortunately, people can die from the worst symptoms.

[ConservativeMind]

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[AbolishCSEU]

It’s never been the same since they took phosphates out of Tide detergent.

[rfp1234]

Eat more fish.

[Jeff Chandler]

I’m running right down to Walgreens to pick up a phosphate level test kit.

[GaltAdonis]

"...It’s never been the same since they took phosphates out of Tide detergent..."

.

Yeah. And those Extra-Phosphate Tide laundry pods were so darn yummy too!

/S