Oncology Central

‘Breakthrough Therapy’ shows promise in acute lymphoblastic leukemia

Results published last week in The New England Journal of Medicine demonstrate that an investigational personalized cellular therapy termed CTL019 promoted responses and remission in 90% of patients who had suffered multiple relapses of acute lymphoblastic leukemia (ALL).

In the study, which was carried out at the Perelman School of Medicine at the University of Pennsylvania (PA, USA), infusions of engineered ‘hunter’ cells (CTL019) resulted in complete remission in 27 of the 30 patients studied and 78% were alive 6 months subsequent to treatment.

“The patients who participated in these trials had relapsed as many as four times; including 60% whose cancers came back even after stem cell transplants. Their cancers were so aggressive they had no treatment options left,” commented senior author of the study Stephan Grupp of the Perelman School of Medicine and Children’s Hospital of Philadelphia. “The durable responses we have observed with CTL019 therapy are unprecedented.”

CTL019 is manufactured from a patient’s own T cells, which are then reprogrammed using a gene transfer technique that causes them to attack tumor cells. The modified T cells contain a chimeric antigen receptor, an antibody-like protein that can attach to the CD19 protein found on the surface of B cells, including those that characterize several leukemia types.

Once the cells have been modified, they are infused back into the patient where they then multiply rapidly due to a signaling domain built into the chimeric antigen receptor. Tests have revealed that more than 10,000 new tumor-killing cells can be formed for each single engineered cell patients receive.

The patient follow-up periods in the study ranged from 1.4–24 months, with most exceeding 6 months. Of the total study group, five patients sought alternate therapy and seven patients relapsed between 6 weeks and 8.5 months after their infusions, including three whose cancers returned as CD19-negative ALL that could not be treated with CTL019. Currently 19 patients remain in remission, 15 with the CTL019 therapy alone, including one individual who was the first patient to receive the therapy more than 2 years ago.

Through additional tests involving patients in complete remission it was demonstrated that along with malignant cells, their normal noncancerous B cells, which express the CD19 protein, had also been eliminated. This absence of normal B cells for an extended time period following CTL019 treatment indicates continuing activity of the modified T cells, therefore providing potentially long-term prevention of tumor recurrence.

“Our results support that CTL019 can produce long-lasting remissions for certain heavily pretreated ALL patients without further therapy,” explained Noelle Frey of the University of Pennsylvania Abramson’s Cancer Center, co-first author of the study. “For our patients who have already relapsed after stem cell transplants, or don’t have any options for donors, this option has provided new hope.”

These successes have resulted in CTL019 being elected as a Breakthrough Therapy by the US FDA, the first personalized cellular therapy to receive the designation.

Sources: Penn Medicine press release




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