Long-Term Treatment With Selective PI3Kδ Inhibitor Leniolisib in Adults With Activated PI3Kδ Syndrome
The result's identifiers
Result code in 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>
Alternative codes found
RIV/00216208:11130/24:10479279
Result on the web
<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>
Alternative languages
Result language
angličtina
Original language name
Long-Term Treatment With Selective PI3Kδ Inhibitor Leniolisib in Adults With Activated PI3Kδ Syndrome
Original language description
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.).
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30102 - Immunology
Result continuities
Project
—
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2024
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Blood Advances
ISSN
2473-9529
e-ISSN
2473-9537
Volume of the periodical
8
Issue of the periodical within the volume
12
Country of publishing house
US - UNITED STATES
Number of pages
17
Pages from-to
3092-3108
UT code for WoS article
001255347700001
EID of the result in the Scopus database
2-s2.0-85197291465