Session: 112. Thalassemia and Globin Gene Regulation: Poster III
Hematology Disease Topics & Pathways:
Research, Biological therapies, Clinical Research, Thalassemia, Hemoglobinopathies, patient-reported outcomes, Diseases, Gene Therapy, Therapies
Methods: Pts with TDT underwent hematopoietic stem progenitor cell collection followed by myeloablative busulfan conditioning and beti-cel infusion. TI is defined as weighted average Hb ≥9 g/dL without packed red blood cell transfusions for ≥12 months. Generic health related QoL (HRQoL) over time was assessed using the Pediatric Quality of Life Inventory (PedsQL; range, 0-100) for pediatric and adolescent pts (<18 years old [YO]). Short Form-36 Health Survey Physical Component Summary and Mental Component Summary (SF-36 PCS and MCS, respectively; range 0-100), and the EuroQol (EQ-5D-3L) visual analog scale (VAS; range 0-100) composite index score (range 0-1) for adult (≥18 YO) pts. HRQoL was assessed at baseline (BL), Months (M) 6, 12, 18, 24 (in the parent HGB studies), and M 36, 48, and 60 (in LTF-303) after beti-cel infusion. Pts were excluded from HRQoL analyses if BL or M36 HRQoL assessment was missing as of data cut (Aug 2021). Higher scores indicated improvement in HRQoL. A bespoke questionnaire assessing β-thalassemia and pt-centric aspects of daily living (i.e., ability to work or attend school, physical activity, and perceived benefit from treatment) was completed at M 36.
Results: As of August 18, 2021, 57 pts were enrolled in LTF-303 (phase 1/2: 22 pts; phase 3: 35 pts), of which 26 (45.6%) were pediatric / adolescent pts and 31 (54.4%) were adult pts. Among pts <18 YO with PedsQL data who achieved TI, the mean (standard error (SE)) PedsQL total score (population norm = 80.9) increased from 77.4 (3.4) at BL (n=19) to 92.1 (4.2) at M 36 (n=4). Among adult pts with SF-36 data who achieved TI, the mean (SE) SF-36 PCS and MCS scores (US general population norm = 50) increased from 53.8 (1.4) and 50.9 (1.7), respectively, at BL (n=12) to 55.7 (1.7) and 56.3 (1.4) at M 36 (n=9), respectively. The mean (SE) EQ-5D-3L Composite Index and VAS scores increased from 0.92 (0.04) and 85.2 (3.0), respectively, at BL (n=12), to 0.95 (0.03) and 91.4 (2.2) at M 36 (n=9) (Table 1). Data from the M 36 testimonial questionnaire (Figure 1) showed the ability to seek employment or be employed, increased from 68.8% (11/16) of pts at BL to 93.8% (15/16) at M 36. There was a reduction in school absences at M 36 (44.4% [4/9] missing school) compared with BL (83.3% [15/18] missing school). 50% (10/20) of pts still required management of disease symptoms at M 36. 80% (16/20) of pts reported improvement in physical activity at M 36. 100% (19/19) of pts reported an overall benefit from undergoing treatment with beti-cel.
Conclusions: Published data shows beti-cel is potentially curative in pts with TDT, defined as having TI with normal or near-normal Hb. It was previously shown that with high-range QoL at BL, QoL improved at 1-2 years post-beti-cel. The updated data indicates durability of QoL improvement through year 3. A trend towards a positive impact on employment, school attendance, physical activity, and other aspects of life is also observed.
Disclosures: Locatelli: Novartis: Honoraria, Speakers Bureau; Jazz Pharmaceuticals: Honoraria; Medac: Speakers Bureau; SOBI: Speakers Bureau; Miltenyi: Speakers Bureau; BlueBird bio: Speakers Bureau; Amgen: Speakers Bureau; Neovii: Speakers Bureau. Walters: BioLabs, Inc.: Consultancy; Vertex Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Ensoma, Inc.: Consultancy, Current holder of stock options in a privately-held company; AllCells, Inc.: Consultancy. Kwiatkowski: Agios: Consultancy; bluebird bio, Inc.: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy; Celgene: Consultancy; Imara: Consultancy, Research Funding; Forma: Consultancy, Research Funding; Chiesi: Consultancy; Silence Therapeutics: Consultancy; Apopharma: Research Funding; Bioerativ: Research Funding; Sangamo: Research Funding; Biomarin: Consultancy; CRISPR/Vertex: Research Funding. Cavazzana: Smart-Immune: Current Employment, Current equity holder in private company; Cellectis: Consultancy; Noga: Consultancy. Porter: Protagonism: Honoraria; Celgene: Consultancy, Honoraria; bluebird bio: Consultancy, Honoraria; VIFOR: Honoraria; Silence Therapeutics: Honoraria; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees; La Jolla Pharmaceuticals: Honoraria; Agios: Consultancy, Honoraria; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees. Thrasher: Orchard Therapeutics: Consultancy; Rocket Pharmaceuticals: Consultancy; 4bio capital: Consultancy; Generation Bio: Consultancy, Current equity holder in publicly-traded company. Kulozik: Vertex: Honoraria; BMS: Honoraria; bluebird bio, Inc.: Honoraria, Research Funding; Celgene: Honoraria. Thuret: bluebird bio, Inc.: Other: Participation to clinical trials; Celgene: Other: Participation to clinical trials; Novartis pharma: Other: Participation to clinical trials; Vertex Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees. Rasko: Genea: Current equity holder in publicly-traded company; Rarecyte: Current equity holder in private company; Gilead, Roche, Novartis, Bluebird Bio, SPARK therapeutics, Cynata, Pfizer Inc: Consultancy. Yannaki: Pfizer: Speakers Bureau. Ali: bluebird bio, Inc.: Current Employment. Thakar: bluebird bio, Inc.: Current Employment. Gruppioni: bluebird bio, Inc.: Current Employment. Thompson: Global Blood Therapeutic: Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; Editas: Research Funding; Biomarin: Research Funding; Baxalta: Research Funding; CRISPR/Vertex: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy, Research Funding; bluebird bio, Inc.: Consultancy, Research Funding; Beam: Consultancy; Agios: Consultancy; Novartis: Research Funding.
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