Long-Term Treatment With Selective PI3Kδ Inhibitor Leniolisib in Adults With Activated PI3Kδ Syndrome

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064203%3A_____%2F24%3A10479279" target="_blank" >RIV/00064203:_____/24:10479279 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11130/24:10479279

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=4jBoEIWBly" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=4jBoEIWBly</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1182/bloodadvances.2023011000" target="_blank" >10.1182/bloodadvances.2023011000</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Long-Term Treatment With Selective PI3Kδ Inhibitor Leniolisib in Adults With Activated PI3Kδ Syndrome

Popis výsledku v původním jazyce

Activated phosphoinositide 3-kinase delta syndrome (APDS) is an inborn error of immunity that manifests as immune deficiency and dysregulation; symptoms include frequent infections and lymphoproliferation. In our dose-finding and phase 3 placebo-controlled trials, treatment with the selective PI3Kδ inhibitor leniolisib reduced lymphoproliferation and normalized lymphocyte subsets. Here, we present 6 years of follow-up from the 6 adult patients in the original dose-finding trial receiving leniolisib. We used data from the ongoing open-label extension study, which was supplemented at later time points by investigators, including health-related quality of life assessed through a clinician-reported questionnaire. We observed improvements in health-related quality of life: 5/6 patients experienced an increase in physical capabilities and socialization and a decrease in prescribed medications. Immune subsets improved in all patients: mean transitional B-cell levels decreased from 38.17% to 2.47% and the CD4:CD8 T-cell ratio normalized to 1.11. Manifestations seen before and within the first year of leniolisib exposure, such as infections and gastrointestinal conditions, attenuated following year 2 with few new conditions emerging out to year 6. Thrombocytopenia or lymphopenia remained present in half of patients at year 6. Of 83 adverse events through year 5, 90.36% were grade 1; none were grade 4-5 nor deemed leniolisib-related. Collectively, we saw an enhancement in health-related quality of life as well as durable changes in lymphocyte subsets and clinical manifestations, further supporting the use of leniolisib as a long-term therapeutic option for the treatment of APDS. (Funded by Novartis Pharmaceuticals Corporation and Pharming Group NV; ClinicalTrials.gov identifier: NCT02859727.).

Název v anglickém jazyce

Long-Term Treatment With Selective PI3Kδ Inhibitor Leniolisib in Adults With Activated PI3Kδ Syndrome

Popis výsledku anglicky

Activated phosphoinositide 3-kinase delta syndrome (APDS) is an inborn error of immunity that manifests as immune deficiency and dysregulation; symptoms include frequent infections and lymphoproliferation. In our dose-finding and phase 3 placebo-controlled trials, treatment with the selective PI3Kδ inhibitor leniolisib reduced lymphoproliferation and normalized lymphocyte subsets. Here, we present 6 years of follow-up from the 6 adult patients in the original dose-finding trial receiving leniolisib. We used data from the ongoing open-label extension study, which was supplemented at later time points by investigators, including health-related quality of life assessed through a clinician-reported questionnaire. We observed improvements in health-related quality of life: 5/6 patients experienced an increase in physical capabilities and socialization and a decrease in prescribed medications. Immune subsets improved in all patients: mean transitional B-cell levels decreased from 38.17% to 2.47% and the CD4:CD8 T-cell ratio normalized to 1.11. Manifestations seen before and within the first year of leniolisib exposure, such as infections and gastrointestinal conditions, attenuated following year 2 with few new conditions emerging out to year 6. Thrombocytopenia or lymphopenia remained present in half of patients at year 6. Of 83 adverse events through year 5, 90.36% were grade 1; none were grade 4-5 nor deemed leniolisib-related. Collectively, we saw an enhancement in health-related quality of life as well as durable changes in lymphocyte subsets and clinical manifestations, further supporting the use of leniolisib as a long-term therapeutic option for the treatment of APDS. (Funded by Novartis Pharmaceuticals Corporation and Pharming Group NV; ClinicalTrials.gov identifier: NCT02859727.).

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

Blood Advances

ISSN

2473-9529

e-ISSN

2473-9537

Svazek periodika

8

Číslo periodika v rámci svazku

12

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

17

Strana od-do

3092-3108

Kód UT WoS článku

001255347700001

EID výsledku v databázi Scopus

2-s2.0-85197291465