In recent years, chimeric antigen receptor (CAR) T-cell therapies have shown significant success in treating certain blood cancers, inspiring scientists to evolve the therapy model for use in other types of cancer. However, patients may have serious side effects, including cytokine release syndrome, neurotoxicity, and quality of life (QOL) impairments. Adverse effects of CAR T-cell therapy are also associated with neuroinflammatory markers that are upregulated in low socioeconomic status (SES) populations. A new Haematologica study takes a closer look at how living in a low SES environment might impact patients’ immune function and clinical outcomes following CAR T-cell therapy.
“We examined whether patient response to a novel anti-CD20 and anti-CD19 (LV20.19) CAR T-cell treatment was affected by patient SES while exploring several possible biological mechanisms—including cytokines and kynurenine metabolites—that might explain the effects of SES on CAR T-cell therapy outcomes,” said Jennifer Knight, MD, MS, FACLP, Associate Professor, Psychiatry and Behavioral Medicine and Microbiology & Immunology. “We discovered most peak cytokine concentrations and several of the neurotoxic pathway kynurenine metabolites were significantly elevated among patients of lower SES. These patients also experienced earlier onset of cytokine release syndrome and reported more pain and poorer sleep quality.”
Investigators were not surprised by these results, as low SES is consistently associated with both increased inflammatory biology and worse cancer treatment outcomes. However, they did not expect that the effects of these therapies would be robust enough to persist in such a small sample of 15 patients. The team is currently working to develop a more comprehensive, multi-site study to better understand the relationships between adverse socioenvironmental factors, biological indicators of stress, and clinical outcomes among CAR T-cell recipients.