Improvements in health-related quality of life in patients with transfusion-dependent β-thalassemia after exagamglogene autotemcel

Abstract

Transfusion-dependent β-thalassemia (TDT) can have negative impacts on a patient's health-related quality of life (HRQoL). Exagamglogene autotemcel (exa-cel) is a one-time, ex vivo CRISPR-Cas9 gene-edited cell therapy for TDT shown in a phase 3 clinical trial to result in transfusion independence in most participants. Here, we describe changes in patient-reported outcome (PRO) measures after exa-cel infusion in 54 participants (adults, n = 35; adolescents, n = 19), who had ≥16 months of follow-up. In adults, PRO measures included the EuroQol Quality of Life Scale-5 dimensions-5 levels of severity (EQ-5D-5L) and the Functional Assessment of Cancer Therapy Bone Marrow Transplant (FACT-BMT). In adolescents, the EuroQol Quality of Life Scale-5 dimensions-youth (EQ-5D-Y) and Pediatric Quality of Life Inventory (PedsQL) instruments were used. At baseline, mean EQ-5D-5L visual analog scale (VAS) and US and UK health utility index scores in adults were in line with baseline scores reported for adults with TDT. After exa-cel infusion, all 3 scores improved, exceeding established minimal clinically important differences (MCIDs) at month 48. Mean FACT-General (FACT-G) score and bone marrow transplant subscale score improved through month 48, also exceeding MCIDs, with improvements in all 4 FACT-G subscales (physical, social/family, emotional, and functional well-being). Consistent with HRQoL improvements in adults, adolescents had increases from baseline at month 24 in mean EQ-5D-Y VAS score and PedsQL total score, with sustained improvements in both physical and psychosocial health subcomponents. These results indicate exa-cel leads to broad, durable, and clinically meaningful improvements in HRQoL in adults and adolescents with TDT. These trials were registered at www.ClinicalTrials.gov as #NCT03655678 and #NCT04208529.

Graphical abstract

Figure 1.

Changes in FACT-G total and BMTS scores in adults in the primary efficacy set (PES) after exa-cel infusion. (A) Mean change from BL by study visit in FACT-G total score. (B) Mean change from BL by study visit in BMTS score. Red lines in figures depict established MCID range. Error bars indicate the standard error of the mean. BL is defined as the most recent nonmissing measurement (scheduled or unscheduled) collected before the start of mobilization. BL, baseline; SE, standard error.

Figure 2.

Changes in PedsQL total and domain scores in adolescents in the PES after exa-cel infusion. (A) Mean changes in PedsQL total score, psychosocial score, and physical score from BL at months 12 and 24. (B) Mean changes in the psychosocial domains from BL at months 12 and 24. Dotted lines indicate the MCID for each measure. Error bars indicate standard error of the mean. BL is defined as the most recent nonmissing measurement (scheduled or unscheduled) collected before the start of mobilization. ∗Total score summarizes questions from the psychosocial and physical scores. ∗∗Psychosocial score summarizes questions from the emotional, social, and school function domains in panel B.