Betibeglogene autotemcel (beti-cel), a one-time gene therapy, enabled durable transfusion independence in most patients with transfusion-dependent -thalassemia (TDT) who were treated across 4 clinical studies.<\/p>\n
Of 60 patients enrolled overall, 17 of 22 (77%) treated in the 2 phase 1\/2 studies were able to stop packed red blood cell transfusions. In the 2 phase 3 studies, which used a refined manufacturing process resulting in improved beti-cel characteristics, 89% (n = 31\/35) of patients with at least 6 months of follow-up achieved transfusion independence for more than 6 months,1 reported Suradej Hongeng, MD, during the virtual 2021 Transplantation & Cellular Therapy Meetings.<\/p>\n
The median follow-up after beti-cel infusion in the 4 studies has been 24.8 months (range, 1.1-71.8).<\/p>\n
With up to 6 years of follow-up, 1-time beti-cel gene therapy enabled durable transfusion independence in the majority of patients, said Hongeng, from Ramathibodi Hospital of Mahidol University, in Bangkok, Thailand.<\/p>\n
Patients who achieved transfusion independence experienced a 38% median reduction in liver iron concentration (LIC) from baseline to month 48. The median reduction in LIC was 59% in patients with a baseline LIC more than 15 mg\/g dw. A total of 21 of 37 (57%) patients who achieved transfusion independence have stopped iron chelation for 6 months or longer, with a median duration of 18.5 months from stopping iron chelation to last follow-up.<\/p>\n
Erythropoiesis as determined by soluble transferrin receptor level was also improved in transfusion-independent patients. Bone marrow biopsies showed improvement in the myeloid:erythroid ratio.<\/p>\n
Beti-cel adds functional copies of a modified form of the -globin (A-T87Q-globin) gene into a patients own hematopoietic stem cells (HSCs) through transduction of autologous CD34+ cells using a BB305 lentiviral vector. Following single-agent busulfan myeloablative conditioning, beti-cel is infused, after which the transduced HSCs engraft and reconstitute red blood cells containing functional adult hemoglobin derived from the gene therapy.<\/p>\n
Of the 60 patients treated, 43 were genotype non-\/ and 17 were \/ . The median age at consent was 20 years in the phase 1\/2 trials and 15 years in the phase 3 trials. Median LIC at baseline was 7.1 and 5.5 mg Fe\/g dw, respectively, and median cardiac T2 was 34 and 37 msec, respectively. The vector copy number was 0.8 in the phase 1\/2 trial and 3.0 in the phase 3 study. Additionally, 32t and 78t CD34+ cells were transduced, respectively.<\/p>\n
The phase 1\/2 studies showed promising results but lower achievement of transfusion independence in patients with the \/ genotype, leading to a refinement in the manufacturing process, which resulted in a higher number of transduced cells and a higher number of vector copy number, said Hongeng.<\/p>\n
The median time to neutrophil engraftment was 22.5 days and the median time to platelet engraftment was 44 days. Lymphocyte subsets were generally within the normal range after beti-cel infusion, which is different from allogeneic stem cell [transplantation], which is probably around 6 months to a year to get complete recovery of immune reconstitution, he said. The median duration of hospitalization was 42 days.<\/p>\n
All patients were alive at the last follow-up (March 3, 2020). Eleven of 60 (18%) of patients experienced at least 1 adverse event (AE) considered related or possibly related to beti-cel, the most common being abdominal pain (8%) and thrombocytopenia (5%). Serious AEs were those expected after myeloablative conditioning: veno-occlusive liver disease (8%), neutropenia (5%), pyrexia (5%), thrombocytopenia (5%), and appendicitis, febrile neutropenia, major depression, and stomatitis (3% each).<\/p>\n
Of the 7 patients experiencing veno-occlusive liver disease, 3 were of grade 4 and 2 were of grade 3. Two other patients had grade 2 veno-occlusive disease. There were no cases of insertional oncogenesis.<\/p>\n
Persistent vector-positive hematopoietic cells and durable HbaT87Q levels supported stable total hemoglobin over time. In phase 3 trials, the median peripheral blood vector copy number was 1.2 c\/dg at month 12 and 2.0 c\/dg at month 24, and the median total hemoglobin was 11.5 g\/dL at month 12 and 12.9 g\/dL at month 24.<\/p>\n
The weighted average of hemoglobin during transfusion independence in the phase 1\/2 trials was 10.4 g\/dL, and patients were transfusion-independent for a median of 51.2 months. In the phase 3 studies, the weighted average of hemoglobin during transfusion independence was 11.9 g\/dL, and patients were transfusion-independent for a medium 17.7 months.<\/p>\n
Hongeng S, Thompson AA, Kwiatkowski JL, et al. Efficacy and safety of betibeglogene autotemcel (beti-cel; LentiGlobin for -thalassemia) gene therapy in 60 patients with transfusion-dependent -thalassemia (TDT) followed for up to 6 years post-infusion. Presented at: 2021 Transplantation & Cellular Therapy Meetings; February 8-12, 2021; virtual. Abstract 1.<\/p>\n
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Beti-Cel Gene Therapy Frees Patients With Beta-Thalassemia From Red Blood Cell Transfusions - OncLive<\/a><\/p>\n","protected":false},"excerpt":{"rendered":" Betibeglogene autotemcel (beti-cel), a one-time gene therapy, enabled durable transfusion independence in most patients with transfusion-dependent -thalassemia (TDT) who were treated across 4 clinical studies. Of 60 patients enrolled overall, 17 of 22 (77%) treated in the 2 phase 1\/2 studies were able to stop packed red blood cell transfusions. Continue reading