• Franco Locatelli, Alexis A Thompson, Janet L Kwiatkowski, John B Porter, Adrian J Thrasher, Suradej Hongeng, Martin G Sauer, Isabelle Thuret, Ashutosh Lal, Mattia Algeri, Jennifer Schneiderman, Timothy S Olson, Ben Carpenter, Persis J Amrolia, Usanarat Anurathapan, Axel Schambach, Christian Chabannon, Manfred Schmidt, Ivan Labik, Heidi Elliot, Ruiting Guo, Mohammed Asmal, Richard A Colvin, and Mark C Walters.
• From IRCCS Ospedale Pediatrico Bambino Gesù, Sapienza, University of Rome, Rome (F.L., M. Algeri); Ann and Robert H. Lurie Children's Hospital of Chicago, Northwestern University, Chicago (A.A.T., J.S.); Children's Hospital of Philadelphia and Perelman School of Medicine at the University of Pennsylvania, Philadelphia (J.L.K., T.S.O.); University College London Hospital (J.B.P., B.C.) and University College London Great Ormond Street Institute of Child Health and Great Ormond Street Hospital NHS Trust (A.J.T., P.J.A.) - all in London; Ramathibodi Hospital, Mahidol University, Bangkok, Thailand (S.H., U.A.); the Department of Pediatric Hematology, Oncology, and Stem Cell Transplantation in Children (M.G.S.) and the Institute of Experimental Hematology (A.S.), Hannover Medical School, Hannover, and GeneWerk, Heidelberg (M.S., I.L.) - both in Germany; Hôpital de la Timone (I.T.) and Institut Paoli-Calmettes Comprehensive Cancer Center (C.C.) - both in Marseille, France; the University of California, San Francisco, Benioff Children's Hospital, Oakland (A.L., M.C.W.); and the Division of Hematology-Oncology, Boston Children's Hospital, Harvard Medical School, Boston (A.S.), and Bluebird Bio, Cambridge (H.E., R.G., M. Asmal, R.A.C.) - all in Massachusetts.
• N. Engl. J. Med. 2022 Feb 3; 386 (5): 415-427.

BackgroundBetibeglogene autotemcel (beti-cel) gene therapy for transfusion-dependent β-thalassemia contains autologous CD34+ hematopoietic stem cells and progenitor cells transduced with the BB305 lentiviral vector encoding the β-globin (βA-T87Q) gene.MethodsIn this open-label, phase 3 study, we evaluated the efficacy and safety of beti-cel in adult and pediatric patients with transfusion-dependent β-thalassemia and a non-β0/β0 genotype. Patients underwent myeloablation with busulfan (with doses adjusted on the basis of pharmacokinetic analysis) and received beti-cel intravenously. The primary end point was transfusion independence (i.e., a weighted average hemoglobin level of ≥9 g per deciliter without red-cell transfusions for ≥12 months).ResultsA total of 23 patients were enrolled and received treatment, with a median follow-up of 29.5 months (range, 13.0 to 48.2). Transfusion independence occurred in 20 of 22 patients who could be evaluated (91%), including 6 of 7 patients (86%) who were younger than 12 years of age. The average hemoglobin level during transfusion independence was 11.7 g per deciliter (range, 9.5 to 12.8). Twelve months after beti-cel infusion, the median level of gene therapy-derived adult hemoglobin (HbA) with a T87Q amino acid substitution (HbAT87Q) was 8.7 g per deciliter (range, 5.2 to 10.6) in patients who had transfusion independence. The safety profile of beti-cel was consistent with that of busulfan-based myeloablation. Four patients had at least one adverse event that was considered by the investigators to be related or possibly related to beti-cel; all events were nonserious except for thrombocytopenia (in 1 patient). No cases of cancer were observed.ConclusionsTreatment with beti-cel resulted in a sustained HbAT87Q level and a total hemoglobin level that was high enough to enable transfusion independence in most patients with a non-β0/β0 genotype, including those younger than 12 years of age. (Funded by Bluebird Bio; HGB-207 ClinicalTrials.gov number, NCT02906202.).Copyright © 2021 Massachusetts Medical Society.

39 keywords...

hide…