Toxicity of Asciminib in Real Clinical Practice: Analysis of Side Effects and Cross-Toxicity with Tyrosine Kinase Inhibitors.

Abstract

(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.

• Authors: 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, Valentín García-Gutiérrez
• Journal: Cancers (Cancers (Basel)) Vol. 15 Issue 4 (Feb 07 2023) ISSN: 2072-6694 [Print] Switzerland
• PMID: 36831388 (Publication Type: Journal Article)