TOPLINE:

Exagamglogene autotemcel (exa-cel), a CRISPR-Cas9 gene-edited cell therapy, led to sustained improvements in health-related quality of life (HRQOL) for both adults and adolescents with transfusion-dependent beta thalassemia (TDT). Patient-reported outcomes showed clinically meaningful enhancements across physical, emotional, and social domains following treatment.

METHODOLOGY:

• A total of 54 participants (35 adults and 19 adolescents) with TDT who had at least 16 months of follow-up were evaluated for changes in patient-reported outcome measures following exa-cel infusion.
• Patient-reported outcomes in adults were assessed using the EuroQOL 5-dimensions 5-levels of severity (EQ-5D-5L) and the Functional Assessment of Cancer Therapy-Bone Marrow Transplant instruments.
• Adolescent participants completed the EQ-5D Youth and Pediatric QOL Inventory (PedsQL) assessments to measure HRQOL outcomes.
• Analysis included follow-up data for up to 48 months in adults and up to 24 months in adolescents from the CLIMB THAL-111 Phase 3 trial and CLIMB-131 extension study.

TAKEAWAY:

• Adults showed improvements in EQ-5D-5L visual analog scale scores from baseline (mean difference, 14.0; standard deviation, 25.4) at month 48, exceeding the minimal clinically important difference of 7-10 points.
• Mean Functional Assessment of Cancer Therapy-General scores and Bone Marrow Transplant subscale scores in adults improved through month 48, surpassing minimal clinically important differences across all subscales.
• Adolescents showed sustained improvements in EQ-5D-Youth visual analog scale scores and PedsQL total scores (mean difference, 6.1; standard deviation, 16.4) and (mean difference, 12.2; standard deviation, 11.8) respectively at month 24.
• Both physical and psychosocial health components showed improvements in adolescents (mean difference, 12.4; standard deviation, 15.5) and (mean difference, 12.0; standard deviation, 10.4) respectively at month 24.

IN PRACTICE:

“These results indicate exa-cel leads to broad, durable, and clinically-meaningful improvements in HRQOL in adults and adolescents with TDT,” the authors of the study wrote.

SOURCE:

The study was led by Franco Locatelli, MD, PhD, IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy. It was published online in Blood Advances.

LIMITATIONS:

According to the authors, the patient-reported outcome tools used were not specifically developed for patients with TDT. The established minimal clinically important differences were derived from other hematologic conditions rather than being disease-specific. Additionally, the EQ-5D-5L instrument may lack content validity for fully capturing disease burden in these patients. The researchers also noted that trends over time should be interpreted cautiously due to the changing sample sizes and smaller numbers at longer follow-up periods.

DISCLOSURES:

The study was designed by Vertex Pharmaceuticals in collaboration with academic authors. Franco Locatelli disclosed having ties with Amgen, Bluebird Bio, Gilead, Jazz Pharmaceuticals, Medac, Miltenyi, Neovii, Novartis, Sanofi, SOBI, and Vertex. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.