1. Cytoreductive treatment in patients with CALR-mutated essential thrombocythaemia: a study comparing indications and efficacy among genotypes from the Spanish Registry of Essential Thrombocythaemia.
- Author
-
Alvarez-Larrán A, Angona A, Andrade-Campos M, Soledad Noya M, Teresa Gómez-Casares M, Cuevas B, Caballero G, García-Hernández C, García-Gutiérrez V, Palomino A, Ferrer-Marín F, Isabel Mata-Vázquez M, Moretó A, Magro E, Murillo I, Manuel Alonso-Domínguez J, María Guerra J, Guerrero L, María Raya J, Pérez-Encinas M, Carreño-Tarragona G, Fox L, Pastor-Galán I, Bellosillo B, and Hernández-Boluda JC
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Amino Acid Substitution, Child, Female, Follow-Up Studies, Humans, Janus Kinase 2 genetics, Male, Middle Aged, Spain, Calreticulin genetics, Genotype, Hydroxyurea administration & dosage, Mutation, Missense, Quinazolines administration & dosage, Registries, Thrombocythemia, Essential drug therapy, Thrombocythemia, Essential genetics
- Abstract
The present study assessed the criteria for initiating cytoreduction and response to conventional therapies in 1446 patients with essential thrombocythemia (ET), 267 (17%) of which were CALR-mutated. In low risk patients, time from diagnosis to cytoreduction was shorter in CALR-positive than in the other genotypes (2·8, 3·2, 7·4 and 12·5 years for CALR, MPL, JAK2V617F and TN, respectively, P < 0·0001). A total of 1104 (76%) patients received cytoreductive treatment with hydroxycarbamide (HC) (n = 977), anagrelide (n = 113), or others (n = 14). The estimated cumulative rates of complete haematological response (CR) at 12 months were 40 % and 67% in CALR and JAK2V617F genotypes, respectively. Median time to CR was 192 days for JAK2V617F, 343 for TN, 433 for MPL, and 705 for CALR genotypes (P < 0·0001). Duration of CR was shorter in CALR-mutated ET than in the remaining patients (P = 0·003). In CALR-positive patients, HC and anagrelide had similar efficacy in terms of response rates and duration. CALR-mutated patients developed resistance/intolerance to HC more frequently (5%, 23%, 27% and 15% for JAK2V617F, CALR, MPL and TN, respectively; P < 0·0001). In conclusion, conventional cytoreductive agents are less effective in CALR-mutated ET, highlighting the need for new treatment modalities and redefinition of haematologic targets for patients with this genotype., (© 2020 British Society for Haematology and John Wiley & Sons Ltd.)
- Published
- 2021
- Full Text
- View/download PDF