Driving Progress in CAR-T Therapy

Chimeric antigen receptor T-cell (CAR-T) therapy can provide durable remissions for patients with relapsed or refractory B-cell lymphomas, but when the treatment fails these patients have limited options and poor survival. Investigators now report phase 1 safety and efficacy results for an investigational anti-CD19 CAR-T modified (“armored”) to express human interleukin-18 (IL-18). Patients who were resistant to or had relapse after prior anti-CD19 CAR-T therapy, and who remained CD19 positive on biopsy, received a single infusion of the huCART19-IL18 at five dose levels ranging from 3×10⁶ to 3×10⁸. Most received bridging therapy before CAR-T infusion. Patients with incomplete remission or later relapse during the study could receive a repeat CAR-T dose.

All dose levels resulted in CAR T-cell expansion and treatment response, including in patients with large B-cell, follicular, and mantle cell lymphomas. Among 21 patients infused, the overall response rate was 81% and the complete response rate was 52%. Response was greater with prior CD28-based than with prior 4-1BB–based CAR-T. The median duration of response was 9.6 months; 3 patients have remained in remission for more than 2 years. Cytokine release syndrome occurred in 13 patients (10 grade 1–2; 3 grade 3) and immune effector cell-associated neurotoxicity syndrome in 3 patients (all grade 1–2).