LentiGlobin for Sickle Cell Has Potential to Improve Health-Related Quality of Life

December 6, 2020
Jonathan Alicea

Patients with baseline PROMIS-57 scores worse than population norms reported clinically significant improvements in 6 of 8 domains at 12 months post-treatment.

Findings from a new study suggested that LentiGlobin improved health-related quality of life metrics for patients with sickle cell disease. The study was presented this weekend at the American Society of Hematology (ASH) 2020 Conference.

Julie Kanter, MD, University of Alabama at Birmingham, led a team that evaluated patient-reported quality of life outcomes 12 months post-treatment from the ongoing phase 1/2 HGB-206 study, which is currently assessing the safety and efficacy of LentiGlobin for sickle cell disease gene therapy.

So far, the most recently treated cohort of patients have improved in laboratory assessments. Results indicated a trend towards normalization in key hemolysis markers as well as an improvement in total hemoglobin values. The ongoing study also reported near resolution of vaso-occlusive crises and acute chest syndrome (ACS). Thus, the authors considered these findings to suggest that the therapy has a fundamental effect on sickle cell pathophysiology.

Patients enrolled in the study were ≥12 and ≤50 years of age and had a history of stroke or severe vaso-occlusive events. Those with acute episodes of pain and acute chest syndrome were also included.

In addition to assessing laboratory and clinical markers, investigators also evaluated patient-reported outcomes using the PRO Measurement Information System (PROMS)-57.

“PROMIS-57 assesses HRQoL using collection of short forms containing 8 questions for each of the 7 PROMIS domains (Depression, Anxiety, Pain Interference, Fatigue, Sleep Disturbance, in which a lower score denotes improvement, and Physical Function, Satisfaction with Participation in Social Roles, in which a higher score denotes improvement) and a 0–10 Pain Intensity numeric rating scale (NRS). PROMIS-57 has been validated in patients with SCD,” Kanter and colleagues explained.

Thus, the team analyzed data for 10 patients from the most recently treated cohort. Using baseline scores and population norms, the investigators then stratified the patients into 2 sub-groups. One sub-group consisted of those with baseline scores considered “worse” than the population norm, and the other group was for those with baseline scores “better” than the norm.

The population norm was for Pain Intensity was 2.6, while the T-score for all other domains was 50.

Minimal clinically importance difference was defined as 2-point difference for pain intensity and 5-point difference for all other domains.

LentiGlobin Leads to Improved Quality of Life Measures

Results showed that patients with a baseline score “worse” than the population norm reported improvements in all domains at month 6 and were sustain through month 12. Further, these patients reported clinically meaningful improvements in 6 of the 8 domains.

At baseline, the mean T-score for pain intensity was 6 and decreased to 2.4 at month 12 (5 patients reported improvements).

Similar trends were reported for Pain Interference (n = 7), which saw a decrease from 63 to 48; Anxiety (n = 3), which decreased from 62 to 48; Depression (n = 4), which decreased from 62 to 44; Satisfaction with Social Roles (n = 5), which increased from 39 to 60; and Physical Function (n = 4), which improved from 40 to 56.

For those who had baseline scores that were “better” than or near the population norm, clinically meaningful improvements were reported in Physical Function (n = 6), which increased from 49 at baseline to 55 at month 12, and Fatigue (n = 9), which decreased from 50 to 43.

Although they acknowledged these results were indeed encouraging, they nonetheless believed that larger sample sizes are need to validate and clarify to impact of the therapy on some PROMIS-57 domains.

The study, “Improvements in Health-Related Quality of Life for Patients Treated with LentiGlobin for Sickle Cell Disease (bb1111) Gene Therapy,” was presented at ASH 2020.