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CAR T-cell therapy shows significant benefit in pediatric ALL
SAN FRANCISCO — A complete response rate of more than 90% was reported for a cohort of patients with pediatric acute lymphoblastic leukemia who were treated with chimeric antigen receptor T-cell therapy.
Stephan A. Grupp, MD, PhD, professor of Pediatrics at the University of Pennsylvania Perelman School of Medicine and director of Translational Research at the Center for Childhood Cancer Research at Children's Hospital of Philadelphia, presented findings for 39 pediatric patients with ALL treated with CD19-directed CAR t-cell product, or CTL019. “The idea is that we have to collect T-cells from each patient, so this is very much an individualized therapy,” Grupp said. “It allows activation of the T-cell.”
Stephan A. Grupp
The median follow-up duration was 6 months. “Some went out to a year, and the longest was 31 months,” Grupp said.
Results indicated a complete response rate of 92%. Thirty-six of 39 patients were in complete response within 28 days of T-cell infusion, according to Grupp.
After 12 months, there have been no relapse events. Three patients have subsequently undergone stem cell transplantation. “This is not a bridge to transplant,” Grupp said.
Of the 10 relapses, five patients were CD19-positive and five patients were CD19-negative.
Treatment responses were 82% for patients with >50% blasts and 88% for patients with >5% blasts, according to Grupp. “If you look at the response rate, it is statistically similar in each of these groups,” he said. “The response rate seems to be within the limitation of the statistical design of the study independent of the disease burden, which is a key point here.”
Grupp also discussed the durability of this intervention. “Persistence of the cells is a key point,” he said. “After we give them, they stick around for many months in many patients. About two-thirds of patients retain their T-cells for 2 months or longer. This is key to maintaining remission in these patients.”
“Proliferation of these cells is enormous,” he added.
Other results indicated a 6-month duration of response of 76% (95% CI, 61-94) and a 6-month EFS of 70% (95% CI, 56-88).
Regarding toxicities, Grupp noted that CTL019 is associated with B-cell aplasia and a significant risk of cytokine-release syndrome.
For more information:
Grupp SA. Abstract #380. Presented at: ASH Annual Meeting and Exhibition; Dec. 6-9, 2014; San Francisco.
Disclosure: Grupp reports consulting and research funding associations with Novartis.
Perspective
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One caveat on immune therapy, particularly with the successes of the CD19-targeted therapies, is that when you really rev up the immune response, there is some toxicity. Ultimately, we will have to try to balance how much to excite the immune system. But I see this approach as a way forward to revolutionizing the treatment of hematologic cancers.
The other very exciting thing about the CAR T-cell field is that there has been a lot of interest from pharma. We will start seeing more centralized manufacturing models, where the product will be manufactured and shipped out to various centers. That model is totally feasible. Not all cell therapeutic strategies will fit that model, but if pharma remains invested in this, it will broaden applicability in the shortest time frame.