Cancers (Feb 2023)

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

  • 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

DOI
https://doi.org/10.3390/cancers15041045
Journal volume & issue
Vol. 15, no. 4
p. 1045

Abstract

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(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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