Interim analysis: Open-label extension study of leniolisib for patients with APDS

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung


  • V. Koneti Rao - , National Institutes of Health (NIH) (Autor:in)
  • Elaine Kulm - , Leidos Inc (Autor:in)
  • Anna Šedivá - , Karlsuniversität Prag (Autor:in)
  • Alessandro Plebani - , University of Brescia (Autor:in)
  • Catharina Schuetz - , Klinik und Poliklinik für Kinder- und Jugendmedizin (Autor:in)
  • Anna Shcherbina - , Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology (Autor:in)
  • Virgil A. Dalm - , Erasmus University Medical Center, Erasmus University Rotterdam (Autor:in)
  • Antonino Trizzino - , ARNAS Civico Di Cristina Benfratelli Hospital (Autor:in)
  • Yulia Zharankova - , Belarusian Research Center for Pediatric Oncology (Autor:in)
  • Sharon Webster - , National Institutes of Health (NIH) (Autor:in)
  • Alanvin Orpia - , National Institutes of Health (NIH) (Autor:in)
  • Julia Körholz - , Klinik und Poliklinik für Kinder- und Jugendmedizin, Technische Universität Dresden (Autor:in)
  • Vassilios Lougaris - , University of Brescia (Autor:in)
  • Yulia Rodina - , Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology (Autor:in)
  • Kath Radford - , Novartis Pharmaceuticals UK Ltd (Autor:in)
  • Jason Bradt - , Alphabet Inc. (Autor:in)
  • Anurag Relan - , Alphabet Inc. (Autor:in)
  • Steven M. Holland - , National Institutes of Health (NIH) (Autor:in)
  • Michael J. Lenardo - , National Institutes of Health (NIH) (Autor:in)
  • Gulbu Uzel - , National Institutes of Health (NIH) (Autor:in)


Background: Activated phosphoinositide 3-kinase delta (PI3Kδ) syndrome (APDS; or p110δ-activating mutations causing senescent T cells, lymphadenopathy, and immunodeficiency) is an inborn error of immunity caused by PI3Kδ hyperactivity. Resultant immune deficiency and dysregulation lead to recurrent sinopulmonary infections, herpes viremia, autoimmunity, and lymphoproliferation. Objective: Leniolisib, a selective PI3Kδ inhibitor, demonstrated favorable impact on immune cell subsets and lymphoproliferation over placebo in patients with APDS over 12 weeks. Here, we report results from an interim analysis of an ongoing open-label, single-arm extension study. Methods: Patients with APDS aged 12 years or older who completed NCT02435173 or had previous exposure to PI3Kδ inhibitors were eligible. The primary end point was safety, assessed via investigator-reported adverse events (AEs) and clinical/laboratory evaluations. Secondary and exploratory end points included health-related quality of life, inflammatory markers, frequency of infections, and lymphoproliferation. Results: Between September 2016 and August 2021, 37 patients (median age, 20 years; 42.3% female) were enrolled. Of these 37 patients, 26, 9, and 2 patients had previously received leniolisib, placebo, or other PI3Kδ inhibitors, respectively. At the data cutoff date (December 13, 2021), median leniolisib exposure was 102 weeks. Overall, 32 patients (87%) experienced an AE. Most AEs were grades 1 to 3; none were grade 4. One patient with severe baseline comorbidities experienced a grade 5 AE, determined as unrelated to leniolisib treatment. While on leniolisib, patients had reduced annualized infection rates (P =.004), and reductions in immunoglobulin replacement therapy occurred in 10 of 27 patients. Other observations include reduced lymphadenopathy and splenomegaly, improved cytopenias, and normalized lymphocyte subsets. Conclusions: Leniolisib was well tolerated and maintained durable outcomes with up to 5 years of exposure in 37 patients with APDS. identifier: NCT02859727.


Seiten (von - bis)265-274.e9
FachzeitschriftJournal of allergy and clinical immunology
PublikationsstatusVeröffentlicht - Jan. 2024

Externe IDs

PubMed 37797893
Mendeley 7e702755-e470-3b84-8d83-7a01ec7ae21a
ORCID /0009-0003-6519-0482/work/147142932
ORCID /0000-0001-6313-4434/work/147143699



  • APDS, B cells, PI3Kδ inhibitor, PIK3CD, PIK3R1, T cells, clinical trial, long-term safety, lymphoproliferation, primary immunodeficiency, Class I Phosphatidylinositol 3-Kinases/genetics, Humans, Male, Lymphadenopathy/complications, Young Adult, Quality of Life, Adult, Female, Mutation, Phosphatidylinositol 3-Kinases/genetics, Immunologic Deficiency Syndromes/genetics