Hemoglobinopathies

At the 63rd annual meeting of the American Society of Hematology, investigators presented (abstract 7) promising findings regarding patient-reported quality-of-life (QoL) outcomes up to 24 months after LentiGlobin infusion among patients in Group C of the HGB-206 study in sickle cell disease (SCD). For the study, patients 12 to 50 years of age with severe SCD and recurrent severe vaso-occlusive events (VOEs) underwent plerixafor mobilization and apheresis followed by myeloablative busulfan conditioning and LentiGlobin infusion. In earlier evaluations of this ongoing phase 1/2 multicenter trial evaluating efficacy and safety of LentiGlobin for SCD (bb1111) gene therapy, patients in Group C experienced complete resolution of severe VOEs, near-normalization of key hemolysis markers, and normalization of total hemoglobin up to 24 months after receiving LentiGlobin. This gene therapy also yielded clinically meaningful improvements in QoL for adult patients.

In the current QoL evaluation, in addition to undergoing clinical and laboratory assessments, patients were surveyed using PROMIS-57, a short-form patient-reported outcomes measurement information system QoL monitoring tool that has been validated in SCD. This instrument is used to gather information on 7 PROMIS domains (Depression, Anxiety, Pain Interference, Fatigue, Sleep Disturbance, Physical Function, and Satisfaction with Participation in Social Roles) and includes a 0–10 Pain Intensity numeric rating scale (NRS). Available data were analyzed for 25 of 35 Group C patients (median age, 25 years; 40% female) who completed PROMIS-57 assessments at baseline, with up to 24 months of follow-up as of mid February 2021. Group C patients with baseline scores "worse" than the population norm reported improvements in all domains at Month 6 up to Month 24. Importantly, mean pain interference decreased from 64.2 (n=16) to 44.5 (n=5), pain intensity decreased from 6.5 (n=15) to 1.8 (n=5) from baseline to Month 24, and fatigue decreased from 64.6 (n=8) to 46.9 (n=1) from baseline to Month 18. Among patients with baseline scores "better or near" the population norm, scores generally remained stable through Month 24. Values for patients overall showed meaningful change in all domains and in the Pain Intensity NRS, with the exception of Anxiety. Investigators concluded that, while the study is limited by its sample size, the data "show LentiGlobin for SCD not only improved hematologic parameters and resulted in complete resolution of severe VOEs, as presented elsewhere, but also provided [a] sustained and clinically meaningful QoL benefit for patients."