Interim Analysis: Open-Label Extension Study of Leniolisib for Patients with APDS

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064203%3A_____%2F24%3A10470183" target="_blank" >RIV/00064203:_____/24:10470183 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11130/24:10470183

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=7Yg-CmEW6K" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=7Yg-CmEW6K</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.jaci.2023.09.032" target="_blank" >10.1016/j.jaci.2023.09.032</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Interim Analysis: Open-Label Extension Study of Leniolisib for Patients with APDS

Popis výsledku v původním jazyce

BACKGROUND: Activated phosphoinositide 3-kinase delta (PI3Kδ) syndrome (APDS; or p110δ-activating mutations causing senescent T cells, lymphadenopathy, and immunodeficiency; PASLI) 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 &gt;=12 years who completed NCT02435173 or had prior exposure to PI3Kδ inhibitors were eligible. The primary endpoint is safety, assessed via investigator-reported adverse events and clinical/laboratory evaluations. Secondary and exploratory endpoints include 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 - consisting of 26, 9 and 2 patients who previously received leniolisib, placebo or other PI3Kδ inhibitors, respectively. At the data cut-off (13 Dec 2021), median leniolisib exposure was 102 weeks. Overall, 32 patients (87%) experienced an AE; most AEs were grades 1-3, none were grade 4. One patient with severe baseline comorbidities experienced a grade 5 AE, determined unrelated to leniolisib treatment. While on leniolisib, patients had reduced annualized infection rates (p=0.004) and reductions in immunoglobulin replacement therapy occurred in 10/27 patients. Other observations include reduced lymphadenopathy and splenomegaly, improved cytopenias and normalized lymphocyte subsets. CONCLUSION: Leniolisib was well-tolerated and maintained durable outcomes with up to 5-years exposure in 37 patients with APDS.

Název v anglickém jazyce

Interim Analysis: Open-Label Extension Study of Leniolisib for Patients with APDS

Popis výsledku anglicky

BACKGROUND: Activated phosphoinositide 3-kinase delta (PI3Kδ) syndrome (APDS; or p110δ-activating mutations causing senescent T cells, lymphadenopathy, and immunodeficiency; PASLI) 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 &gt;=12 years who completed NCT02435173 or had prior exposure to PI3Kδ inhibitors were eligible. The primary endpoint is safety, assessed via investigator-reported adverse events and clinical/laboratory evaluations. Secondary and exploratory endpoints include 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 - consisting of 26, 9 and 2 patients who previously received leniolisib, placebo or other PI3Kδ inhibitors, respectively. At the data cut-off (13 Dec 2021), median leniolisib exposure was 102 weeks. Overall, 32 patients (87%) experienced an AE; most AEs were grades 1-3, none were grade 4. One patient with severe baseline comorbidities experienced a grade 5 AE, determined unrelated to leniolisib treatment. While on leniolisib, patients had reduced annualized infection rates (p=0.004) and reductions in immunoglobulin replacement therapy occurred in 10/27 patients. Other observations include reduced lymphadenopathy and splenomegaly, improved cytopenias and normalized lymphocyte subsets. CONCLUSION: Leniolisib was well-tolerated and maintained durable outcomes with up to 5-years exposure in 37 patients with APDS.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30102 - Immunology

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2024

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Journal of Allergy and Clinical Immunology

ISSN

0091-6749

e-ISSN

1097-6825

Svazek periodika

153

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

10

Strana od-do

265-274

Kód UT WoS článku

001167750600001

EID výsledku v databázi Scopus

2-s2.0-85174673820