Symptom Changes in Pediatric Patients with Activated Phosphoinositide 3-Kinase Delta Syndrome (APDS) Receiving Leniolisib

IntroductionActivated Phosphoinositide 3-Kinase Delta Syndrome (APDS) is a rare disease characterized by progressive symptoms that begin early in life, including lymphoproliferation, recurrent and persistent infections, and early mortality compared with the global population. Delayed diagnosis and inadequate treatment in childhood may exacerbate disease manifestations. This post hoc analysis evaluated caregiver-reported changes in APDS symptoms in pediatric patients after 12 weeks of treatment with leniolisib.MethodsTwenty-one pediatric patients aged 4–11 years with APDS received open-label leniolisib in a single-arm, multicenter, international study (NCT05438407). Study documents received institutional review board approval. In a post hoc analysis, worst-rated dimension scores on the APDS-Symptom Severity Scale (APDS-SSS) at baseline were compared with week 12 scores. Item-level symptom scores, assessed by APDS-SSS, rated moderate to very severe (≥2 on a 0–4 scale) at baseline, were also compared with week 12 scores. Multiple scores per participant were reported in the event of within-person ties.ResultsAfter 12 weeks of leniolisib treatment, APDS-SSS symptom severity scores for dimensions with the worst-rated baseline scores generally decreased, indicating improvement. All patients with infections (n = 4) or gastrointestinal symptoms (n = 3) as their worst baseline dimension improved after 12 weeks of treatment. Among patients with respiratory symptoms as their worst baseline dimension, 10 of 13 (77%) improved at week 12; 1 remained stable, and 2 worsened to mild/moderate severity over time.Among patients with emotional impact as their worst baseline dimension, 3 of 6 (50%) improved at week 12; 1 remained stable, and 2 worsened to mild severity over time. Item-level symptom severity also generally decreased over time. For 3 symptoms, 1 patient each improved from severe/very severe at baseline to “none” at 12 weeks. All patients with visible swollen lymph nodes (n = 3) improved: 1 from severe to moderate and 2 from moderate to none.ConclusionAccording to caregiver ratings, the most severe APDS-related symptoms experienced by pediatric patients aged 4–11 years showed improvements after 12 weeks of leniolisib treatment. These results demonstrate the potential clinical benefit of leniolisib in most pediatric patients.