SAN DIEGO – A bioengineered T-cell therapy elicited complete responses without inducing graft-versus-host disease in 13 of 16 children with relapsed or refractory precursor B-cell acute lymphoblastic leukemia, reported Dr. David M. Barrett of the Children’s Hospital of Philadelphia.
The findings expand on the researchers’ initial study of 2 patients, published earlier this year (N. Engl. J. Med. 2013;368:1509-18). The treatment has now been given to 16 children aged 5-22 years (median, 9.5 years) with relapsed or refractory precursor B-cell acute lymphoblastic leukemia (B-ALL) that was positive for the B-lymphocyte antigen CD19.
For the phase I trial, each patient’s T cells were modified to create chimeric T cells (CTL019 cells) that are directed at B cells bearing the CD19 antigen, Dr. Barrett reported at Pediatric Cancer at the Crossroads.
In the week before the CTL019 infusions, 13 of the 16 patients underwent chemotherapy. On the day before the infusions, 14 of the 16 patients had evidence of active or minimal residual disease.
CTL019 was administered over 1-3 days. There were no infusion toxicities higher than grade 2; however, three patients developed fevers within 24 hours and did not receive additional infusions. At peak T-cell expansion, all responding patients developed some degree of delayed cytokine-release syndrome. A subset of these patients also had transient hypotension and hypoxia. Tocilizumab, an anti–IL-6 receptor antagonist, reversed the hemodynamic and respiratory instability; in some of the patients, corticosteroids were concurrently administered.
A complete response occurred in 13 patients, including 1 patient with CD19+ T-cell ALL; 3 patients did not respond to treatment.
During 1.2-16 months of follow-up (median, 3.4 months), bone marrow complete responses persisted in 10 of the 16 patients. Three patients initially had complete responses and relapsed; one was negative for CD19.
In patients with ongoing responses, complete B-cell aplasia occurred 1-15 months post infusion. No unusual infections were noted in patients given intravenous immunoglobulin to restore immune function, Dr. Barrett said at the meeting, which was sponsored by the American Association for Cancer Research.
While in remission, one child subsequently developed a myelodysplastic syndrome with a new trisomy 8. In another patient, a single leukemia cutis lesion occurred at 6 months post infusion.
The University of Pennsylvania and Novartis have an exclusive global research and licensing agreement to study and commercialize the chimeric antigen receptor immunotherapy CTL019. Dr. Barrett did not report disclosures. A coauthor in the study is a Novartis staff member.