Improvements in Health-Related Quality of Life in Patients with Severe Sickle Cell Disease After Exagamglogene Autotemcel

Abstract

Severe sickle cell disease (SCD), an inherited blood disorder characterized by recurrent vaso-occlusive crises (VOCs), has substantial negative impact on 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 (PRO) measures in 30 adults and 12 adolescents who had ≥16 months follow-up in CLIMB SCD-121. Adult PRO measures included 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 health utility US and UK index and EQ 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-G total and BMTS. 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. (CLIMB SCD-121 and 131; Clinical Trials.gov numbers NCT03745287 and NCT04208529).