2026-04-17T21:32:41Zhttps://recercat.cat/oai/request

oai:recercat.cat:11351/137772025-10-24T10:31:10Zcom_2072_378070com_2072_378040col_2072_378092

Refractoriness to eltrombopag in adult primary immune thrombocytopenia: utility of next-generation sequencing techniques GONZALEZ LOPEZ, TOMAS JOSE Sánchez Pérez, Ricardo Pastoriza, Carmen Bernat Pablo, Silvia Fernandez-Fuertes, Fernando Olivera, Pável E. Seqüència de nucleòtids Trombocitopènia - Tractament Antígens CD CHEMICALS AND DRUGS::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Receptors, Cell Surface::Receptors, Immunologic::Receptors, Cytokine::Receptors, Thrombopoietin Other subheadings::Other subheadings::Other subheadings::/agonists DISEASES::Hemic and Lymphatic Diseases::Hematologic Diseases::Blood Platelet Disorders::Thrombocytopenia Other subheadings::Other subheadings::Other subheadings::/drug therapy ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Investigative Techniques::Genetic Techniques::Sequence Analysis::High-Throughput Nucleotide Sequencing COMPUESTOS QUÍMICOS Y DROGAS::aminoácidos, péptidos y proteínas::proteínas::proteínas de membranas::receptores de superficie celular::receptores inmunológicos::receptores de citocinas::receptores de trombopoyetina Otros calificadores::Otros calificadores::Otros calificadores::/agonistas ENFERMEDADES::enfermedades hematológicas y linfáticas::enfermedades hematológicas::trastornos de las plaquetas sanguíneas::trombocitopenia Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::técnicas de investigación::técnicas genéticas::análisis de secuencias::secuenciación de nucleótidos de alto rendimiento Eltrombopag; Primary immune thrombocytopenia; Next-generation sequencing Eltrombopag; Trombocitopenia inmunitaria primaria; Secuenciación de próxima generación Eltrombopag; Trombocitopènia immunitària primària; Seqüenciació de nova generació Thrombopoietin receptor agonists, for example eltrombopag, are standard second-line treatment for immune thrombocytopenia (ITP). Eltrombopag has demonstrated high response rates, both in clinical trials and in routine practice studies. However, some patients with ITP are refractory to this drug. Next-generation sequencing (NGS) may help us identify underlying molecular biology variants that may be involved in eltrombopag refractoriness. Our multicenter national NGS study investigated 110 genes of the most important cell-signaling pathways involved in the mechanism of action of eltrombopag in 35 refractory cases and 35 eltrombopag-responsive controls. Our refractory population comprised 51.4% men with a median age at diagnosis of 48 (range, 38-69) years and a median platelet count of 7 × 109/μL (range, 4 × 109/μL to 16 × 109/μL). At eltrombopag initiation, 78.3% had chronic ITP with a median platelet count of 8 × 109/μL (range, 5× 109/μL to 30 × 109/μL). Treatment with eltrombopag was maintained for a median of 3 (range, 1-9) months before discontinuation. No major grade 3-4 side effects were observed. Several statistical differences were observed in relation to the control responders. Of the total sum of the NGS variants found, 13 variants with statistical significance (P ≤ .05) between case and controls were observed. Two of these have been shown to be associated with cancer. Seven variants are considered benign. Four variants are not previously described, and their significance is unknown. To our knowledge, none of the 13 variants described here has ever been correlated with ITP or eltrombopag refractoriness. Further studies are required to establish their role in this setting. This research was funded by a Novartis Research grant (CETB115BES06T). 2025-10-24T10:31:10Z 2025-10-24T10:31:10Z 2025-10-24T10:31:10Z 2025-10-06T07:21:05Z 2025-10-06T07:21:05Z 2025-08 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://hdl.handle.net/11351/13777 Blood Vessels, Thrombosis & Hemostasis;2(3) https://doi.org/10.1016/j.bvth.2025.100061 Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess Elsevier Scientia