Optimizing CAR T-cell therapy in NHL
“The main message is that you can treat patients with non-Hodgkin’s lymphoma with CAR T cells and get very good response rates with optimization of the CAR T-cell dose and lymphodepletion,” said study author Cameron Turtle, MBBS, PhD, of the Fred Hutchinson Cancer Research Center.
“Strategies like modifying the lymphodepletion in conjunction with suitable CAR T-cell dosing can have a big impact on clinical outcome.”
Safety
Two patients who were treated with the highest CAR T-cell dose (2 × 107 cells/kg) died—1 of pontine hemorrhage and 1 of gastrointestinal hemorrhage associated with a known gastrointestinal invasive lymphomatous mass.
This dose was also associated with an increased risk of severe CRS and neurotoxicity, as was the Cy/Flu regimen.
Twenty patients (62.5%) developed CRS, and 4 (12.5%) had severe CRS. All 4 of these patients had received Cy/Flu.
Nine patients (28%) developed severe neurotoxicity (grade 3 or higher), 7 of whom had received Cy/Flu.
Three of the 6 patients (50%) treated at 2 × 107 CAR-T cells/kg after Cy/Flu developed severe CRS, and 4 of the 6 patients (67%) developed severe neurotoxicity.
The researchers looked for biomarkers of toxicity in serum collected 1 day after CAR T-cell infusion.
They found that high IL-6, IL-8, IL-10, IL-15, and IFN-γ concentrations were associated with subsequent severe CRS and neurotoxicity, and low TGF-Β concentration was associated with neurotoxicity.
The team said these findings provide an opportunity for studying the use of serum cytokine concentrations to identify patients at the highest risk of toxicity who might benefit from early interventions. 
