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Anti-CD19 T cells show promise in adult, pediatric ALL
NEW ORLEANS — Engineered CTL019 cells underwent robust in vivo expansion and induced response in adult and pediatric patients with relapsed and refractory acute lymphoblastic leukemia, according to study results presented at the ASH Annual Meeting and Exposition.
Stephan A. Grupp, MD, PhD, of The Children’s Hospital of Philadelphia, Abramson Cancer Center and Perelman School of Medicine at the University of Pennsylvania in Philadelphia, and colleagues genetically engineered T cells to express an anti-CD19 single chain variable fragment coupled to CD3-zeta signaling and 4-1BB costimulatory domains.
Stephan A. Grupp
“We’re genetically engineering T cells collected from each individual patient using a lentiviral vector — an activated form of the HIV virus — which puts a gene in the cells,” Grupp said during a press conference. “That genetic modification allows the cell to produce these artificial chimeric antigen receptor proteins, which allows the T cell to go after the cancer cell and hopefully kill it. The cells that are made with this technology are extremely active and behave in ways we think are favorable within the patients.”
Grupp and colleagues evaluated the CTL019 cells in 16 children (median age, 9.5 years) and four adults (median age, 50 years) with CD19+ ALL.
Seventeen patients received lymphodepleting chemotherapy the week prior to CTL019 treatment.
The targeted T-cell dose range was 107 to 108 cells/kg, and the targeted transduction efficiency ranged from 11% to 45%. A median 3.7 x 106 CTL019 cells/kg were infused over 1 to 3 days, according to researchers.
Median follow-up was 2.6 months (range, 1-15).
Overall, 14 patients (82%) achieved a complete response, and three patients did not respond. Three additional patients are pending evaluation.
Three patients who achieved complete response 1 month after infusion have since relapsed. One of these patients had CD19-negative disease.
Researchers observed delayed cytokine release syndrome in all patients, with concurrent peak T-cell expansion and fever and variable degrees of myalgias, nausea and anorexia. Researchers also observed hypotension and hypoxia.
There were no cases of graft-versus-host disease in 11 patients who underwent prior allogeneic stem cell transplantation.
Researchers detected CTL019 cells and corresponding B-cell aplasia in patients with ongoing responses for 1 to 15 months after infusion.
“Our results serve as another important milestone in demonstrating the potential of this treatment for patients who truly have no other therapeutic options,” Grupp said. “These data also demonstrate that these engineered hunter cells greatly expand and then persist in patients, allowing for long-term disease control. This allays previous concerns that infused cells only survive for a limited time. In the relatively short time that we’ve observed these patients, we have reason to believe that this treatment could become a viable therapy for their relapsed, treatment-resistant disease, and we look forward to continuing to evaluate their long-term response.”
For more information:
Grupp SA. Abstract #67. Presented at: ASH Annual Meeting and Exhibition; Dec. 7-10, 2013; New Orleans.
Disclosure: Researchers report research funding from, royalties on cell and gene therapy IP patents licensed to, employment with and equity ownership in Novartis.