Outcomes of chronic myeloid leukemia patients after therapeutic failure to conventional tyrosine kinase inhibitors and asciminib
Copyright policy )Outcomes of chronic myeloid leukemia patients after therapeutic failure to conventional tyrosine kinase inhibitors and asciminib
Patients with chronic myeloid leukemia (CML) who have failed conventional tyrosine kinase inhibitors (cTKIs) and asciminib constitute a complex group of patients with few therapeutic options. A retrospective descriptive multicenter observational study was carried out including patients with CML who had presented a therapeutic failure to ≥ 2 cTKIs and asciminib, and had received or were not candidates to ponatinib. Of the 19 patients enrolled, 8 patients failed asciminib due to intolerance and 11 due to resistance. The most common strategy for intolerant patients was to initiate a previously administered cTKI (6/8) with dose adjustments or symptomatic management of adverse events (AEs). Of the patients who failed due to resistance, only patients who underwent progenitor transplantation achieved profound long-term responses. A frequent strategy was to use ponatinib (4/11) in patients previously considered non-candidates, with poor responses in patients in whom dose reductions were used, and severe AEs in patients at standard doses. In the remaining patients, cTKIs and other agents (interferon, hydroxyurea, citarabine, busulfan) were used with poor responses. Patients who progressed to advanced stages had a dismal prognosis. With a median follow-up of 11.2 months, overall survival of the global cohort was 73%; 100% for intolerant patients, 71% for resistant patients and 25% for those who discontinue asciminib in accelerated/blastic phase.
Male, Adult, Niacinamide, CHEMICALS AND DRUGS::Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Enzyme Inhibitors::Protein Kinase Inhibitors, Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia, FENÓMENOS Y PROCESOS::fenómenos fisiológicos::fenómenos farmacológicos y toxicológicos::fenómenos farmacológicos::resistencia a medicamentos::resistencia a los antineoplásicos, Resistance, COMPUESTOS QUÍMICOS Y DROGAS::acciones y usos químicos::acciones farmacológicas::mecanismos moleculares de acción farmacológica::inhibidores enzimáticos::inhibidores de proteínas cinasas, Conventional tyrosine kinase inhibitors, Tyrosine Kinase Inhibitors, DISEASES::Neoplasms::Neoplasms by Histologic Type::Leukemia::Leukemia, Myeloid::Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Proteïnes quinases - Inhibidors - Ús terapèutic - Efectes secundaris, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Humans, Treatment Failure, ENFERMEDADES::neoplasias::neoplasias por tipo histológico::leucemia::leucemia mieloide::leucemia mielogenosa crónica BCR-ABL positiva, Protein Kinase Inhibitors, Resistència als medicaments, Retrospective Studies, Aged, Other subheadings::Other subheadings::Other subheadings::/drug therapy, Real world setting, Leucèmia mieloide crònica - Tractament, ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Diagnosis::Prognosis::Treatment Outcome, Research, Chronic myeloid leukemia, Imidazoles, Asciminib, Middle Aged, Drug Resistance Neoplasm, Intolerance, Pyridazines, TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::diagnóstico::pronóstico::resultado del tratamiento, Treatment Outcome, Drug Resistance, Neoplasm, Avaluació de resultats (Assistència sanitària), Pyrazoles, Female
Male, Adult, Niacinamide, CHEMICALS AND DRUGS::Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Enzyme Inhibitors::Protein Kinase Inhibitors, Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia, FENÓMENOS Y PROCESOS::fenómenos fisiológicos::fenómenos farmacológicos y toxicológicos::fenómenos farmacológicos::resistencia a medicamentos::resistencia a los antineoplásicos, Resistance, COMPUESTOS QUÍMICOS Y DROGAS::acciones y usos químicos::acciones farmacológicas::mecanismos moleculares de acción farmacológica::inhibidores enzimáticos::inhibidores de proteínas cinasas, Conventional tyrosine kinase inhibitors, Tyrosine Kinase Inhibitors, DISEASES::Neoplasms::Neoplasms by Histologic Type::Leukemia::Leukemia, Myeloid::Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Proteïnes quinases - Inhibidors - Ús terapèutic - Efectes secundaris, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Humans, Treatment Failure, ENFERMEDADES::neoplasias::neoplasias por tipo histológico::leucemia::leucemia mieloide::leucemia mielogenosa crónica BCR-ABL positiva, Protein Kinase Inhibitors, Resistència als medicaments, Retrospective Studies, Aged, Other subheadings::Other subheadings::Other subheadings::/drug therapy, Real world setting, Leucèmia mieloide crònica - Tractament, ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Diagnosis::Prognosis::Treatment Outcome, Research, Chronic myeloid leukemia, Imidazoles, Asciminib, Middle Aged, Drug Resistance Neoplasm, Intolerance, Pyridazines, TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::diagnóstico::pronóstico::resultado del tratamiento, Treatment Outcome, Drug Resistance, Neoplasm, Avaluació de resultats (Assistència sanitària), Pyrazoles, Female
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