Most beta thalassemia patients were off transfusions at a median of 26 months after receiving gene therapy via a lentiviral vector, according to new results of two phase 1/2 studies regarding the use of LentiGlobin in transfusion-dependent beta thalassemia.
Of 13 patients who did not have the most severe beta0/beta0 genotype, all but 1 has become transfusion independent post transplant. Among patients who either had the beta0/beta0 genotype or had two copies of the IVS1-110 mutation, transfusions were down a median 73% annually, and three of these patients with more severe thalassemia became transfusion independent.
At the time of last data collection, hemoglobin levels in individual patients ranged from 8.2-13.7 g/dL.
“No clonal dominance related to vector integration was observed,” wrote
Hematopoietic cell transplant (HCT) is an option primarily for younger beta thalassemia patients who have an HLA-matched sibling donor, the researchers wrote in the . Gene therapy represents an alternative to the current standard of care for patients who are not candidates for allogeneic HCT, which – without a good match – carries increased risk for rejection and graft-versus-host disease.
Patients with beta thalassemia aged 35 years or younger and without advanced organ damage were enrolled in the two studies, one conducted internationally and one conducted at a single site in France.
There were some protocol differences between the two studies; notably, the French study used enhanced red cell transfusion for 3 or more months before stem cell mobilization “to enrich for bona fide hematopoietic stem cells in the harvested CD34+ cell compartment by suppressing the erythroid lineage expansion and the skewing that is seen in beta thalassemia,” wrote Dr. Thompson, professor of pediatrics at Northwestern University, Chicago, and her colleagues.