February 2015 Vol 8, Special Issue: Payers' Perspectives in Oncology - Leukemia
Wayne Kuznar

San Francisco, CA—Administration of T-cells engineered with a chimeric antigen receptor (CAR) targeting CD19 (CTL019) persist over the long-term and induce durable remissions in children with relapsed or refractory acute lymphoblastic leukemia (ALL).

In this phase 1/2 study, 92% of patients achieved complete responses (CRs) with CTL019, reported Stephan A. Grupp, MD, PhD, Director of Translational Research, Center for Childhood Cancer Research, the Children’s Hospital of Philadelphia, at ASH 2014.

In July 2014, CTL019 received breakthrough therapy designation from the US Food and Drug Administration as a treatment for pediatric and adult patients with relapsed or refractory ALL.

The CAR process uses genetically modified T-cells to target cancer, explained Dr Grupp. This genetic modification allows the expression of a CAR protein on the surface of the T-cell. The T-cell receptor gains this new recognition capability through the CAR protein, which allows interaction with the cancer cell, with the intent of killing it. It also allows activation of the T-cell, which causes significant proliferation.

More than 130 patients at the University of Pennsylvania and the Children’s Hospital of Philadelphia, encompassing ALL, chronic lymphocytic leukemia, and non-Hodgkin lymphoma, have been treated with CTL019.

Dr Grupp’s report focused on 39 pediatric patients with relapsed, treatment-resistant ALL, who received CTL019 at a median of 3.6 × 106 cells/kg during 1 to 3 days. One week before CTL019 treatment, 87% of patients received lymphodepleting chemotherapy.

CR was achieved in 36 (92%) patients 28 days after T-cell infusion. There have been 10 relapses, 50% related to disappearance of the engineered T-cells (ie, CD19-positive relapse) and 50% related to antigen escape (ie, CD19-negative relapse). Of the patients who relapsed with CD19-positive disease after achieving CR, 40% had disease refractory to previous treatment with blinatumomab.

The median follow-up has been 6 months, but 15 patients have been followed for ≥1 year, with the longest being 31 months. Only 3 patients have subsequently undergone stem-cell transplant.

Response seems to be independent of the disease burden. In patients with >50% bone marrow blasts by minimal residual disease, the overall response rate was 82%, similar to the response rate of 88% in patients with >5% blasts.

The significant risk of treatment is a cytokine-release syndrome, which is higher in patients with high disease burden, although all patients have some degree of cytokine-release syndrome at peak T-cell expansion. “Patients who have <50% bone marrow blasts essentially do not have significant degrees of cytokine-release syndrome,” Dr Grupp noted.

“About two thirds of the patients retain their T-cells for 6 months or longer,” Dr Grupp said. “It’s a key point in terms of maintaining remission in these patients.”

The duration of response has been favorable: 76% of the patients remain in remission if they reach 6-months remission. The event-free survival rate at 6 months is 70%, and the overall survival rate is 75%.

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Last modified: May 4, 2015
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