fa265a46d4d592d9d60ca9c613c1f1fe pmc_9954054.pdf 715d79ceeeb97d7cd02d9945416f1af4d974ef08 pmc_9954054.pdf b7400d7aa1270aecb9b4f927cb0ee372dcb4eb93cd1c5eae90911475339462ff pmc_9954054.pdf Title: Toxicity of Asciminib in Real Clinical Practice: Analysis of Side Effects and Cross-Toxicity with Tyrosine Kinase Inhibitors Subject: (1) Background: Despite the prognostic improvements achieved with tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML), a minority of patients still fail TKIs. The recent introduction of asciminib may be a promising option in intolerant patients, as it is a first-in-class inhibitor with a more selective mechanism of action different from the ATP-competitive inhibition that occurs with TKIs. Therefore, our goal was to analyze toxicities shown with asciminib as well as to study cross-toxicity with previous TKIs. (2) Methods: An observational, multicenter, retrospective study was performed with data from 77 patients with CML with therapeutic failure to second-generation TKIs who received asciminib through a managed-access program (MAP) (3) Results: With a median follow-up of 13.7 months, 22 patients (28.5%) discontinued treatment: 32% (7/22) due to intolerance and 45% (10/22) due to resistance. Fifty-five percent of the patients reported adverse effects (AEs) with asciminib and eighteen percent grade 3–4. Most frequent AEs were: fatigue (18%), thrombocytopenia (17%), anemia (12%), and arthralgias (12%). None of the patients experienced cardiovascular events or occlusive arterial disease. Further, 26%, 25%, and 9% of patients required dose adjustment, temporary suspension, or definitive discontinuation of treatment, respectively. Toxicities under asciminib seemed lower than with prior TKIs for anemia, cardiovascular events, pleural/pericardial effusion, diarrhea, and edema. Cross-toxicity risk was statistically significant for thrombocytopenia, anemia, neutropenia, fatigue, vomiting, and pancreatitis. (4) Conclusion: Asciminib is a molecule with a good safety profile and with a low rate of AEs. However, despite its new mechanism of action, asciminib presents a risk of cross-toxicity with classical TKIs for some AEs. Keywords: asciminib; drug intolerance; toxicities; chronic myeloid leukemia Author: Lucía Pérez-Lamas, Alejandro Luna, Concepción Boque, Blanca Xicoy, Pilar Giraldo, Raúl Pérez López, Concepción Ruiz Nuño, Natalia De las Heras, Elvira Mora Casterá, Javier López Marín, Adrián Segura Díaz, Valle Gómez, Patricia Vélez Tenza, Magdalena Sierra Pacho, Juan Antonio Vera Goñi, Melania Moreno Vega, Alberto Alvarez-Larrán, Montse Cortés, Manuel Pérez Encinas, Patricia Carrascosa Mastell, Anna Angona, Ana Rosell, Sunil Lakhwani, Mercedes Colorado, Elena Ramila, Carlos Cervero, Beatriz Cuevas, Lucía Villalón Blanco, Raquel de Paz, Antonio Paz Coll, María José Fernández, Luis Felipe Casado, Juan Manuel Alonso-Domínguez, María Magdalena Anguita Arance, Araceli Salamanca Cuenca, Antonio Jiménez-Velasco, Santiago Osorio Prendes, Marta Santaliestra, María José Lis Chulvi, Juan Carlos Hernández-Boluda and Valentín García-Gutiérrez Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Tue Feb 7 10:13:02 2023 CET ModDate: Tue Feb 7 10:16:37 2023 CET Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 13 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1387527 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- DGBDNV+VnURWPalladioL-Bold Type 1 Custom yes yes no 10 0 DRZUJM+VnURWPalladioL Type 1 Custom yes yes no 15 0 KGJRNR+URWPalladioL-Bold Type 1 Custom yes yes no 19 0 SFNBSI+URWPalladioL-Roma Type 1 Custom yes yes no 24 0 MERFKE+URWPalladioL-Ital Type 1 Custom yes yes no 28 0 LCJEVJ+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 47 0 PDTLUH+CMSY10 Type 1 Builtin yes yes no 75 0 URYLRZ+URWPalladioL-BoldItal Type 1 Custom yes yes no 79 0 EJNJEM+Calibri,Bold TrueType WinAnsi yes yes no 101 0 EJNDFI+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 104 0 EJNDFK+PalatinoLinotype TrueType WinAnsi yes yes no 107 0 EJNDFM+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 110 0 EJNDFI+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 127 0 EJNDFK+PalatinoLinotype TrueType WinAnsi yes yes no 130 0 EJNDFM+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 133 0 EJNLJA+Calibri TrueType WinAnsi yes yes no 143 0 EJNDFI+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 146 0 EJNDFK+PalatinoLinotype TrueType WinAnsi yes yes no 149 0 EJNDFM+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 152 0 XSCNJY+PalatinoLinotype-Italic TrueType WinAnsi yes yes yes 161 0 MJRELU+PalatinoLinotype-Bold TrueType WinAnsi yes yes yes 165 0 MRPZLU+PalatinoLinotype-Roman TrueType WinAnsi yes yes yes 169 0 EJNLJA+Calibri TrueType WinAnsi yes yes no 180 0 EJNDFI+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 183 0 EJNDFK+PalatinoLinotype TrueType WinAnsi yes yes no 186 0 EJNDFM+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 189 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2023-07-12 02:30:28 CEST RepresentationInformation: pmc_9954054.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2023-03-16 02:18:22 CET Size: 1387527 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 335 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@44c8afef Item: Title: Materials and Methods Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7b69c6ba Item: Title: Results Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@46daef40 Children: Item: Title: Safety Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@12f41634 Item: Title: Cross-Toxicity and Cross Intolerance Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@13c27452 Item: Title: Efficacy Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Item: Title: Discussion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Item: Title: Conclusions Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@50d0686 Info: Title: Toxicity of Asciminib in Real Clinical Practice: Analysis of Side Effects and Cross-Toxicity with Tyrosine Kinase Inhibitors Author: Lucía Pérez-Lamas, Alejandro Luna, Concepción Boque, Blanca Xicoy, Pilar Giraldo, Raúl Pérez López, Concepción Ruiz Nuño, Natalia De las Heras, Elvira Mora Casterá, Javier López Marín, Adrián Segura Díaz, Valle Gómez, Patricia Vélez Tenza, Magdalena Sierra Pacho, Juan Antonio Vera Goñi, Melania Moreno Vega, Alberto Alvarez-Larrán, Montse Cortés, Manuel Pérez Encinas, Patricia Carrascosa Mastell, Anna Angona, Ana Rosell, Sunil Lakhwani, Mercedes Colorado, Elena Ramila, Carlos Cervero, Beatriz Cuevas, Lucía Villalón Blanco, Raquel de Paz, Antonio Paz Coll, María José Fernández, Luis Felipe Casado, Juan Manuel Alonso-Domínguez, María Magdalena Anguita Arance, Araceli Salamanca Cuenca, Antonio Jiménez-Velasco, Santiago Osorio Prendes, Marta Santaliestra, María José Lis Chulvi, Juan Carlos Hernández-Boluda and Valentín García-Gutiérrez Subject: (1) Background: Despite the prognostic improvements achieved with tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML), a minority of patients still fail TKIs. The recent introduction of asciminib may be a promising option in intolerant patients, as it is a first-in-class inhibitor with a more selective mechanism of action different from the ATP-competitive inhibition that occurs with TKIs. Therefore, our goal was to analyze toxicities shown with asciminib as well as to study cross-toxicity with previous TKIs. (2) Methods: An observational, multicenter, retrospective study was performed with data from 77 patients with CML with therapeutic failure to second-generation TKIs who received asciminib through a managed-access program (MAP) (3) Results: With a median follow-up of 13.7 months, 22 patients (28.5%) discontinued treatment: 32% (7/22) due to intolerance and 45% (10/22) due to resistance. Fifty-five percent of the patients reported adverse effects (AEs) with asciminib and eighteen percent grade 3 4. Most frequent AEs were: fatigue (18%), thrombocytopenia (17%), anemia (12%), and arthralgias (12%). None of the patients experienced cardiovascular events or occlusive arterial disease. Further, 26%, 25%, and 9% of patients required dose adjustment, temporary suspension, or definitive discontinuation of treatment, respectively. Toxicities under asciminib seemed lower than with prior TKIs for anemia, cardiovascular events, pleural/pericardial effusion, diarrhea, and edema. Cross-toxicity risk was statistically significant for thrombocytopenia, anemia, neutropenia, fatigue, vomiting, and pancreatitis. (4) Conclusion: Asciminib is a molecule with a good safety profile and with a low rate of AEs. However, despite its new mechanism of action, asciminib presents a risk of cross-toxicity with classical TKIs for some AEs. 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