Hypomethylating agents for patients with VEXAS without myelodysplastic syndrome: Clinical outcome and longitudinal follow-up of vacuolization and UBA1 clonal dynamics

Indexed in

License and use

Citations

Altmetrics

Grant support

This research was supported by Instituto de Salud Carlos III (ISCIII) co-funded by the European Union (FIS PI22/01660 to JE and MDB; Convocatoria d'Intensificacio Interna per als professionals de l'HCB 2023 to MDB); by the Ministerio de Ciencia e Innovacion (MCIN) (PID2021-125106OB-C31); by the Agencia Estatal de Investigacion (AEI) (10.13039/501100011033); and by the Fondo Europeo de Desarrollo Regional (FEDER) (UE to JIA).

Analysis of institutional authors

Mensa-Vilaro, AnnaAuthorJimenez-Vicente, CarlosAuthorDe Landazuri IoAuthorEspinosa, GerardAuthorGuijarro, FrancescaAuthorCortes, AlbertAuthorEsteve, JordiAuthorArostegui, Juan ICorresponding AuthorDiaz-Beya, MarinaCorresponding Author

Publications

Article

Publicated to:British Journal Of Haematology. 206 (2): 565-575 - 2025-01-13 206(2), DOI: 10.1111/bjh.19953

Authors: Alamo, Jose R; Mont-de Torres, Lucia; Castano-Diez, Sandra; Mensa-Vilaro, Anna; Lopez-Guerra, M Monica; Zugasti, Ines; Diaz, Johana; Jimenez-Vicente, Carlos; Plaza, Susana; Fabregat, Virginia; de Landazuri, Inaki Ortiz; Yague, Jordi; Espinosa, Gerard; Sanmarti, Raimon; Rozman, Maria; Guijarro, Francesca; Cortes, Albert; Triguero, Ana; Cardus, Aina; Cuartas, Adriana; Cornejo, Marina; Esteve, Jordi; Arostegui, Juan I; Diaz-Beya, Marina

Affiliations

Ctr Invest Biomed Red Canc CIBERONC, Madrid, Spain - Author

Hosp Clin Barcelona, CDB, Immunol Dept, Barcelona, Spain - Author

Hosp Clin Barcelona, Dept Autoimmune Dis, Barcelona, Spain - Author

Hosp Clin Barcelona, Dept Rheumatol, Barcelona, Spain - Author

Hosp Clin Barcelona, Haematol Dept, Barcelona, Spain - Author

Hosp Clin Barcelona, Pathol Dept, Hematopathol Sect, Barcelona, Spain - Author

Hosp Dr Josep Trueta, ICO, Girona, Spain - Author

Inst Invest Biomed August Pi Sunyer IDIBAPS, Barcelona, Spain - Author

Josep Carreras Leukemia Res Inst, Madrid, Spain - Author

Univ Barcelona, Barcelona, Spain - Author

Abstract

VEXAS syndrome is a haemato-inflammatory disease caused by somatic UBA1 mutations and characterized by cytoplasmic vacuoles in myeloid and erythroid precursor cells. Although there is currently no standard treatment algorithm for VEXAS, patients are generally treated with anti-inflammatory therapies focused on symptom management, with only partial effectiveness. Hypomethylating agents (HMA) have shown promise in VEXAS patients with concomitant myelodysplastic syndrome (MDS), while the efficacy of HMA in VEXAS patients without MDS is largely unknown. Furthermore, the usefulness of monitoring the variant allele frequency (VAF) of UBA1 or vacuolization in precursor cells over the course of treatment has not been extensively investigated. We have evaluated the efficacy of HMA in four VEXAS patients without MDS and performed longitudinal analyses of the VAF of UBA1 and vacuolization during treatment. HMA treatment led to overall clinical improvement, a dramatic reduction in the VAF of UBA1, normalization of haematological and inflammatory markers and a quantifiable decrease in vacuolization, leading us to speculate that unlike anti-inflammatory therapies, HMA may well act as a disease-modifying treatment. If these findings are confirmed in further studies, it could lead to the early use of HMA in the treatment of all VEXAS patients-with or without MDS.

Keywords

<italic>uba1</italic> mutationAgedAzacitidineDna methylationFemaleFollow-up studiesHumansHypomethylating agentsLongitudinal studiesMaleMiddle agedMutationMyelodysplastic syndromeMyelodysplastic syndromesTreatment outcomeUba1 mutationUba1 protein, humanUbiquitin-activating enzymesVacuolesVexas syndromVexas syndrome

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal British Journal Of Haematology due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2025, it was in position 17/97, thus managing to position itself as a Q1 (Primer Cuartil), in the category Hematology.

Impact and social visibility

Leadership analysis of institutional authors

There is a significant leadership presence as some of the institution’s authors appear as the first or last signer, detailed as follows: Last Author (Díaz Beyá, Marina).