Improvements in health-related quality of life in patients with severe sickle cell disease after exagamglogene autotemcel

Severe sickle cell disease (SCD), an inherited blood disorder characterized by recurrent vaso-occlusive crises (VOCs), significantly impairs health-related quality of life (HRQoL). Exagamglogene autotemcel (exa-cel), a one-time, ex vivo CRISPR/Cas9 gene-edited cell therapy, eliminated VOCs in 97% of participants with severe SCD in the phase 3 CLIMB SCD-121 trial. Here, we describe changes in patient-reported outcomes (PROs) in 30 adults and 12 adolescents with ≥16 months follow-up. Adult PROs include EuroQol Quality of Life Scale-5 dimensions-5 levels of severity (EQ-5D-5L), Functional Assessment of Cancer Therapy Bone Marrow Transplant (FACT-BMT), Adult Sickle Cell Quality of Life Measurement Information System (ASCQ-Me), and 11-point pain Numerical Rating Scale (NRS). In adolescents, EuroQol Quality of Life Scale-5 dimensions-youth (EQ-5D-Y), Pediatric Quality of Life Inventory (PedsQL), and pain NRS were used. Adult EQ-5D-5L US and UK healthy utility index and EQ visual analog scale (VAS) scores, which were lower than general population norm at baseline, substantially improved by month 6 after exa-cel infusion and were sustained through month 36, with similar improvements in FACT-General (FACT-G) total and bone marrow transplant subscale. All FACT-G (physical, social/family, emotional, functional well-being) and ASCQ-Me (emotional, social functioning, stiffness, sleep impact) subscales showed clinically meaningful improvement, including ASCQ-Me pain subscales (impact, episode frequency, severity), with substantial decreases in pain episode frequency by month 6. Mean pain NRS score decreased by month 6 and was sustained. Consistent with adults, adolescents had improvements in mean EQ-5D-Y VAS score, PedsQL score, and pain NRS. Exa-cel led to broad and clinically meaningful HRQoL benefits in adults and adolescents with SCD. The CLIMB SCD-121 and CLIMB-131 trials were registered at www.clinicaltrials.gov as #NCT03745287 and #NCT04208529, respectively.

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Journal
Blood Advances
Published
2025-08-26
DOI
https://doi.org/10.1182/bloodadvances.2025016701
Primary Topic
Hemoglobinopathies and Related Disorders
Type
article
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article

Improvements in health-related quality of life in patients with severe sickle cell disease after exagamglogene autotemcel

Markus Y. Mapara, Donna A. Wall, Nanxin Li, Haydar Frangoul et al.
Blood Advances
Hemoglobinopathies and Related Disorders
article

Improvements in health-related quality of life in patients with severe sickle cell disease after exagamglogene autotemcel

Markus Y. Mapara, Donna A. Wall, Nanxin Li, Haydar Frangoul, Franco Locatelli, Lyndsay Molinari, Suzan Imren, Monica Bhatia, Wally R. Smith, Jaime Rubin, Kevin H.M. Kuo, Robert I. Liem, Akshay Sharma, Michael J. Eckrich, Tina Liu, Stephan A. Grupp, William Hobbs, Laurence Dedeken, Puja Kohli
article en

Abstract

Severe sickle cell disease (SCD), an inherited blood disorder characterized by recurrent vaso-occlusive crises (VOCs), significantly impairs health-related quality of life (HRQoL). Exagamglogene autotemcel (exa-cel), a one-time, ex vivo CRISPR/Cas9 gene-edited cell therapy, eliminated VOCs in 97% of participants with severe SCD in the phase 3 CLIMB SCD-121 trial. Here, we describe changes in patient-reported outcomes (PROs) in 30 adults and 12 adolescents with ≥16 months follow-up. Adult PROs include EuroQol Quality of Life Scale-5 dimensions-5 levels of severity (EQ-5D-5L), Functional Assessment of Cancer Therapy Bone Marrow Transplant (FACT-BMT), Adult Sickle Cell Quality of Life Measurement Information System (ASCQ-Me), and 11-point pain Numerical Rating Scale (NRS). In adolescents, EuroQol Quality of Life Scale-5 dimensions-youth (EQ-5D-Y), Pediatric Quality of Life Inventory (PedsQL), and pain NRS were used. Adult EQ-5D-5L US and UK healthy utility index and EQ visual analog scale (VAS) scores, which were lower than general population norm at baseline, substantially improved by month 6 after exa-cel infusion and were sustained through month 36, with similar improvements in FACT-General (FACT-G) total and bone marrow transplant subscale. All FACT-G (physical, social/family, emotional, functional well-being) and ASCQ-Me (emotional, social functioning, stiffness, sleep impact) subscales showed clinically meaningful improvement, including ASCQ-Me pain subscales (impact, episode frequency, severity), with substantial decreases in pain episode frequency by month 6. Mean pain NRS score decreased by month 6 and was sustained. Consistent with adults, adolescents had improvements in mean EQ-5D-Y VAS score, PedsQL score, and pain NRS. Exa-cel led to broad and clinically meaningful HRQoL benefits in adults and adolescents with SCD. The CLIMB SCD-121 and CLIMB-131 trials were registered at www.clinicaltrials.gov as #NCT03745287 and #NCT04208529, respectively.

Blood AdvancesVol. 9(24)
Università Cattolica del Sacro Cuore (IT), Lurie Children's Hospital (US), Morgan Stanley Children's Hospital (US), St. Jude Children's Research Hospital (US), Université Libre de Bruxelles (BE), University Health Network (CA), Children's Hospital of Philadelphia (US), University of Wisconsin–Madison (US), Virginia Commonwealth University (US), University of Toronto (CA), Hospital for Sick Children (CA), Children’s Hospital at TriStar Centennial (US), Sarah Cannon (US), Queen Fabiola Children's University Hospital (BE), New York Oncology Hematology (US), Bambino Gesù Children's Hospital (IT), Lurie Children's Hospital (US), Methodist Children’s Hospital (US), Vertex Pharmaceuticals (United States) (US), Columbia University (US), University of Pennsylvania (US)
Amgen, Bristol-Myers Squibb, Pfizer, Sanofi, Gilead Sciences, Alexion Pharmaceuticals, Vertex Pharmaceuticals, Jazz Pharmaceuticals, Agios Pharmaceuticals, bluebird bio, Incyte, Swedish Orphan Biovitrum, Medac
Openalex Percentile: Top 70%
Hemoglobinopathies and Related Disorders
DOIOpen Access PDFOpenAlex
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