Caregiver- and Clinician-Reported Symptoms in Pediatric Patients with Activated Phosphoinositide 3-Kinase Delta Syndrome (APDS) Receiving Leniolisib

Introduction 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. Methods 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. Results 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. Conclusion 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. Tabular data are included as downloadable supplement files.