Activated Phosphoinositide 3-Kinase Delta Syndrome (APDS) is a rare disease characterized by early-onset, progressive symptoms. Delayed diagnosis and inadequate treatment in childhood may exacerbate disease manifestations and negatively impact health-related quality of life. In a 2-part, open-label, single-arm international study (NCT05438407) evaluating the safety and efficacy of leniolisib in pediatric patients (aged 4–11 years) with APDS, leniolisib was well tolerated, reduced lymphoproliferation, and increased naïve B cells to total B cells at 12 months. Here, we evaluated clinician- and caregiver-reported changes in symptom severity and global impression of change from this study, reporting 3- and 12-month data.
Caregiver- and clinician-reported outcomes were assessed at baseline and after 3 and 12 months of leniolisib treatment. Caregiver assessments included the Caregiver Global Impression of Change-APDS (CaGIC-APDS), APDS-Symptom Severity Scale (APDS-SSS), and Caregiver Overall Treatment Evaluation-APDS (CaOTE-APDS). Clinician assessments included Clinician Global Impression of Change-APDS (CGIC-APDS), Clinician Global Impression of Severity-APDS (CGIS-APDS), and Physician’s Global Assessment (PGA). Study documents received institutional review board approval.
Twenty-one patients were enrolled with a median (range) age of 7 (4–11) years; 61.9% were male. Median (range) treatment compliance baseline to 12 months was 98.7% (25.9%–100.0%). Following 3 and 12 months of treatment, caregiver-reported APDS symptom improvement was assessed with CaGIC-APDS (85.7% and 90.0% of patients, respectively), and clinician-reported improvement was assessed with CGIC-APDS (81.0% and 85.0% of patients, respectively) (supplementary table). Caregivers reported decreases in symptom severity across most APDS-SSS domains from baseline to 3 and 12 months; mean (SD) total symptom score change at 3 months was −0.15 (0.43). Caregivers reported the positive aspects of leniolisib outweighed the negative aspects in 85.7% of patients at 3 months, as assessed by CaOTE-APDS. At 3 and 12 months, clinician-reported mean (SD) changes from baseline indicated improvement, with PGA scores of −18.5 (18.1) and −22.7 (19.7), respectively, and CGIS-APDS scores of −0.5 (0.7) and −0.9 (0.8), respectively.
In pediatric patients receiving leniolisib, caregivers and clinicians reported improvements in symptoms. These findings demonstrated durable and clinically relevant progressive symptom improvement through 12 months.
