A CD19-Directed CAR T-Cell Therapy for Aggressive NHL

A phase I study published in Blood found that treatment with a CD19-specific chimeric antigen receptor (CAR) T-cell therapy was feasible in patients with relapsed/refractory B-cell non-Hodgkin lymphoma (NHL) who had previously received high-dose chemotherapy and underwent autologous hematopoietic cell transplantation (AHCT).

The study included 15 patients (median age, 61 years; range, 34-75 years) with relapsed/refractory B-cell NHL, seven of whom received three or more prior lines of therapy.

Patients underwent infusion with second-generation 19-28z CAR T-cells on days two and three after AHCT. Most patients (n=14) received 5×10⁶ cells/kg, while one received 1×10⁷ cells/kg; however, this patient experienced severe cytokine release syndrome (CRS), so this dose level was not used for other patients.

Survival and toxicities

After a median follow-up of 24 months (range, 12-37 months), four patients remained alive without disease progression. The progression-free survival rate was 40% (95% CI, 20-70) at one year and 30% (95% CI, 20-70) at two years.

The researchers said there was no difference in persistence of CAR T-cell therapy between patients who experienced progression or death (median, 8 days; range, 1-22 days) and those who remained alive with no progression (median, 8 days; range, 6-22 days).

Ten patients (67%) experienced grade 3/4 neurotoxicity and/or seizures after a median of five days (range, 1-6 days) after CAR T-cell infusion. Resolution of these symptoms occurred after a median of 9.5 days (range, 2-20 days).

Six of these patients also developed grade 2-4 CRS at a median of 2.5 days (range, 0-10 days) after infusion. Resolution occurred at a median of eight days (range, 3-12 days).

“Following [high-dose chemotherapy and] AHCT, effector CD4+ and CD8+ immunophenotypes may improve disease control,” the researchers concluded.