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

(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.

Evaluación económica de rituximab en combinación con fludarabinay ciclofosfamida en comparación con fludarabina y ciclofosfamida enel tratamiento de la leucemia linfática crónica / Economic evaluation of rituximab added to fludarabine plus cyclophosphamide versus fludarabine plus cyclophosphamide for the treatment of chronic lymphocytic leukemia

Objetivos: Evaluar el coste-efectividad del esquema de rituximab, fludarabina y ciclofosfamida (R-FC) encomparación con el de fludarabina y ciclofosfamida (FC) en dos tipos de pacientes con leucemia linfáticacrónica (LLC): no tratados previamente o bien en recidiva/resistentes al tratamiento previo.Métodos: Dos modelos de Markov, utilizando los resultados publicados de superviviencia libre de progresión(SLP) de pacientes con LLC tratados con R-FC o FC en primera o segunda línea, las tasas de progresiónde la enfermedad y las tasas de mortalidad en Espa˜na. A los estados de SLP y progresión se les asignaronutilidades obtenidas en un estudio sobre LLC. Los costes de los medicamentos y de los tratamientos desoporte, así como los a˜nos de vida ajustados por calidad (AVAC), se estimaron para un periodo de 10 a˜nos.Se efectuaron análisis de sensibilidad univariados y probabilísticos (Monte Carlo).Resultados: La adición de rituximab a la quimioterapia con FC aumentó los a˜nos de vida ganados (AVG) ylos AVAC tanto en primera como en segunda línea de tratamiento. La razón de coste-eficacia incrementalfue de 20.703 D por AVG y de 19.343 D por AVAC con la primera línea de tratamiento, y de 23.183 D porAVG y 24.781 D por AVAC con la segunda línea de tratamiento.Conclusiones: En los pacientes con LLC no tratados previamente y en aquellos en recaída o resistentes altratamiento previo, la adición de rituximab al esquema FC aumentó la esperanza de vida y los AVAC, y enambos casos resultó ser un tratamiento coste-efectivo (AU)

Objectives: We evaluated the cost-effectiveness of rituximab added to the chemotherapy regimen of fludarabineplus cyclophosphamide (R-FC) versus fludarabine plus cyclophosphamide (FC) for the treatmentof patients with previously untreated or relapsed/refractory chronic lymphocytic leukemia (CLL).Methods: Two Markov models were built, using published results on progression-free survival (PFS) inpatients receiving first- or second-line therapy with R-FC vs FC, rates of disease progression and mortalityrates in Spain. Patient-elicited utilities were applied to PFS and progressed health states. The cost of drugs,supportive care, and quality-adjusted life years (QALY) were estimated over a 10-year period. Univariateand probabilistic (Monte Carlo) sensitivity analyses were performed.Results: The addition of rituximab to chemotherapy in first- and second-line therapy increased lifeyearsgained (LYG) and QALYs compared with chemotherapy. The incremental cost per LYG and QALYgained was D 20,703 and D 19,343 for first-line treatment and was D 23,183 and D 24,781 for second-linetreatment (AU)