Sistema de Salut de Catalunya
[Luna A, Pérez-Lamas L] Hematology Department, Hospital Universitario Ramón y Cajal, IRYCIS, Universidad de Alcala, Madrid, Spain. [Boque C] Institut Catala d’Oncologia, Hospital Duran Y Reynals, L’Hospitalet de Llobregat, Barcelona, Spain. [Giraldo P] Hospital Quirón Zaragoza, Zaragossa, Spain. [Xicoy B] Institut Català d’Oncologia-Hospital Germans Trias I Pujol, Badalona, Spain. [Ruiz Nuño C] Hospital Regional Universitario de Málaga, Málaga, Spain. [Cortes M] Hospital General de Granollers, Granollers, Spain
Hospital General de Granollers
2022-09-13T07:23:20Z
2022-09-13T07:23:20Z
2022-10
Asciminib; Inhibitors; Leukemia
Asciminib; Inhibidors; Leucèmia
Asciminib; Inhibidores; Leucemia
Failure of second-generation tyrosine kinase inhibitors (2GTKI) is a challenging situation in patients with chronic myeloid leukemia (CML). Asciminib, recently approved by the US Federal Drug Administration, has demonstrated in clinical trials a good efficacy and safety profile after failure of 2GTKI. However, no study has specifically addressed response rates to asciminib in ponatinib pretreated patients (PPT). Here, we present data on responses to asciminib from 52 patients in clinical practice, 20 of them (38%) with prior ponatinib exposure. We analyzed retrospectively responses and toxicities under asciminib and compared results between PPT and non-PPT patients.After a median follow-up of 30 months, 34 patients (65%) switched to asciminib due to intolerance and 18 (35%) due to resistance to prior TKIs. Forty-six patients (88%) had received at least 3 prior TKIs. Regarding responses, complete cytogenetic response was achieved or maintained in 74% and 53% for non-PPT and PPT patients, respectively. Deeper responses such as major molecular response and molecular response 4.5 were achieved in 65% and 19% in non-PPT versus 32% and 11% in PPT, respectively. Two patients (4%) harbored the T315I mutation, both PPT.In terms of toxicities, non-PPT displayed 22% grade 3-4 TEAE versus 20% in PPT. Four patients (20% of PPT) suffered from cross-intolerance with asciminib as they did under ponatinib.Our data supports asciminib as a promising alternative in resistant and intolerant non-PPT patients, as well as in intolerant PPT patients; the resistant PPT subset remains as a challenging group in need of further therapeutic options.
Article
Published version
English
Inhibidors enzimàtics; Leucèmia - Tractament; CHEMICALS AND DRUGS::Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Enzyme Inhibitors; DISEASES::Hemic and Lymphatic Diseases::Hematologic Diseases::Bone Marrow Diseases::Myeloproliferative Disorders::Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Other subheadings::Other subheadings::Other subheadings::/drug therapy; COMPUESTOS QUÍMICOS Y DROGAS::acciones y usos químicos::acciones farmacológicas::mecanismos moleculares de acción farmacológica::inhibidores enzimáticos; ENFERMEDADES::enfermedades hematológicas y linfáticas::enfermedades hematológicas::enfermedades de la médula ósea::trastornos mieloproliferativos::leucemia mielogenosa crónica BCR-ABL positiva; Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia
Springer
Annals of Hematology;101
https://doi.org/10.1007/s00277-022-04932-6
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
Articles científics - HG [171]
