ZUMA-1

ZUMA-1 was the pivotal phase 1/2 study of axicabtagene ciloleucel (KTE-C19), a CD19-directed CAR-T, in patients with diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma or transformed follicular lymphoma that was refractory to the last chemotherapy or had relapsed within a year of autologous transplant. Patients received lymphodepleting fludarabine and cyclophosphamide and a single infusion; the primary endpoint was objective response rate.

Most patients responded and more than half achieved a complete response, a striking result in a population whose expected response to salvage chemotherapy was poor, and a large minority remained in durable remission at five years. Cytokine release syndrome and neurological toxicity were frequent but mostly reversible. The product was approved in the United States in October 2017, the first CAR-T for lymphoma, and ZUMA-7 later moved it into second line.