Chimeric antigen receptor-modified t-cells in acute lymphoblastic leukemia

Abstract

Study in 5 adults with relapsed B-cell ALL Brentjens and colleagues found that molecular remission was rapidly induced in patients with relapsed B-cell ALL using autologous T cells modified to express a CD19specific CD28/CD3dual-signaling chimeric antigen receptor (CAR; 19-18z CAR-modified T cells). Five adult patients (age range, 23-66 years) who had not previously received allogeneic hematopoietic stem cell transplantation (HSCT) received the adoptive T-cell therapy after conditioning therapy with cyclophosphamide. Treatment consisted of an infusion of 1.5-3.0 10 autologous 19-18z CAR-modified T cells/kg. Eligible patients subsequently underwent allogeneic HSCT. Of the 5 patients, 2 had persistent chemotherapyrefractory disease after salvage therapy (63% and 70% blasts in bone marrow). Two others had achieved morphologic complete remission (CR) during salvage therapy with evidence of minimal residual disease (MRD) on deep sequencing polymerase chain reaction (PCR) and fluorescence-activated cell sorting (FACS), and 1 patient was MRD negative after salvage therapy. All of the patients were MRD negative on PCR after adoptive T-cell therapy. Of the 2 patients with persistent refractory disease after salvage therapy, 1 achieved morphologic CR by day 11 after T-cell infusion and MRD-negative status by day 59, and the other achieved both morphologic CR and MRD-negative status by day 8. Of the 2 other MRD-positive patients, 1 was MRD negative by day 28 and the other was MRD negative at day 30 and remained MRD negative up to the time of allogeneic HSCT at 122 days. Four patients underwent allogeneic HSCT at 1 to 4 months after T-cell therapy. One patient, who was ineligible for allogeneic HSCT (due to multiple pre-existing comorbidities) and additional T-cell therapy, relapsed at