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Activated phosphoinositide 3-kinase delta (PI3Kδ) syndrome (APDS) is an ultra-rare, progressive genetic disease, characterised by immune deficiency and dysregulation, affecting individuals from birth. In a 12-week phase III randomised placebo-controlled trial, leniolisib, a selective PI3Kδ inhibitor, was well-tolerated and met both co-primary endpoints (change from Baseline in log10-transformed sum of product of diameters of index lymph nodes and percentage of naïve/total B cells at Day 85). Here, prespecified subgroup analyses are reported in adolescents aged 12-17 years (leniolisib, n = 8; placebo, n = 4) and adults aged ≥18 (leniolisib, n = 13; placebo, n = 6). In both subgroups, leniolisib reduced lymphadenopathy (least squares mean change versus placebo: adolescents, -0.4 versus -0.1; adults, -0.3 versus 0.1) and increased the percentage of naïve B cells (least squares mean change: adolescents, 44.5 versus -16.5; adults, 28.4 versus -1.1). Leniolisib was well-tolerated in both adolescents and adults. These results show leniolisib is an effective APDS treatment in both subpopulations. PLAIN LANGUAGE SUMMARY: What is activated PI3Kδ syndrome (APDS)? APDS is an ultra-rare disease in which the immune system does not work correctly. People with APDS have a wide range of symptoms, including infections, certain organs associated with the immune system becoming larger, and worse quality of life. These symptoms generally start in childhood. Why was this study carried out? Current treatments only treat the symptoms of APDS, rather than correcting the cause of the problem. These treatments can also have significant side effects. A new medication for APDS called leniolisib aims to treat the underlying cause of the disease. This publication reports results from a clinical trial of leniolisib which compared patients who received leniolisib with patients who received a placebo. The aim of this report was to examine these clinical trial results to understand if leniolisib is effective and safe when treating both adolescents (12-17 years old) and adults (18 years and older) with APDS. What were the results of this study? Leniolisib improved the number of certain immune cells, compared to patients who did not receive leniolisib, in both adolescents and adults with APDS. Leniolisib also reduced the size of the enlarged immune system organs in both adolescents and adults with APDS. There were no major safety concerns for either age group who received leniolisib. What do these results mean? These results show that leniolisib can help the immune system to work in a way that is closer to those without APDS. This new treatment is effective and generally well-tolerated for both adolescents and adults. These results indicate that people with APDS are able to start treatment with leniolisib during adolescence, which may slow the build-up of symptoms and may also have a positive impact on the quality of their lives.
- MeSH
- B-lymfocyty imunologie účinky léků MeSH
- dítě MeSH
- dospělí MeSH
- dvojitá slepá metoda MeSH
- fosfatidylinositol-3-kinasy třídy I * genetika antagonisté a inhibitory MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- primární imunodeficience * farmakoterapie genetika MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze III MeSH
- randomizované kontrolované studie MeSH
Infectious complications are an important cause of morbidity and mortality in patients with myelodysplastic syndromes (MDS). Preventing infections could significantly improve both survival and quality of life. Unfortunately, both infections and antimicrobial prophylaxis in patients with MDS are incompletely assessed due to the heterogeneity of disorders included in each publication, changing definitions over time, and lack of standardized prophylaxis practices. Despite these limitations, some basic statements can be made. Infections in MDS are associated with neutropenia. Patients with lower-risk (LR) MDS tend to have fewer infections compared to patients with higher-risk (HR) MDS, which may be related to the different prevalence of neutropenia in the 2 groups. Pneumonia is the most common infection, and bacteria are the most common pathogens. Invasive fungal infections (IFI) are uncommon. Reactivation of latent viruses are rare. With the limited data available, we agree that antibacterial prophylaxis can be considered in patients with HR-MDS during severe neutropenia and early cycles of therapy when infections are most likely to occur. Given the low prevalence of IFI and viral reactivation, antimicrobial prophylaxis for these pathogens is less likely to be advantageous for most patients, although antifungal prophylaxis with activity against mold is commonly used in patients with persistent, profound neutropenia. Ultimately, improved data collection regarding infections and antimicrobial prophylaxis is needed to improve care for patients with MDS.
In March 2021, following the annual International Committee on Taxonomy of Viruses (ICTV) ratification vote on newly proposed taxa, the phylum Negarnaviricota was amended and emended. The phylum was expanded by four families (Aliusviridae, Crepuscuviridae, Myriaviridae, and Natareviridae), three subfamilies (Alpharhabdovirinae, Betarhabdovirinae, and Gammarhabdovirinae), 42 genera, and 200 species. Thirty-nine species were renamed and/or moved and seven species were abolished. This article presents the updated taxonomy of Negarnaviricota as now accepted by the ICTV.
- MeSH
- lidé MeSH
- Mononegavirales * MeSH
- viry * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
In March 2020, following the annual International Committee on Taxonomy of Viruses (ICTV) ratification vote on newly proposed taxa, the phylum Negarnaviricota was amended and emended. At the genus rank, 20 new genera were added, two were deleted, one was moved, and three were renamed. At the species rank, 160 species were added, four were deleted, ten were moved and renamed, and 30 species were renamed. This article presents the updated taxonomy of Negarnaviricota as now accepted by the ICTV.
- MeSH
- Mononegavirales klasifikace MeSH
- terminologie jako téma MeSH
- Publikační typ
- zprávy MeSH
