Cytoreductive treatment in patients with CALR-mutated essential thrombocythaemia: a study comparing indications and efficacy among genotypes from the Spanish Registry of Essential Thrombocythaemia

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 wereCALR-mutated. In low risk patients, time from diagnosis to cytoreduction was shorter inCALR-positive than in the other genotypes (2 center dot 8, 3 center dot 2, 7 center dot 4 and 12 center dot 5 years forCALR,MPL,JAK2V617F and TN, respectively,P < 0 center dot 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% inCALRandJAK2V617F genotypes, respectively. Median time to CR was 192 days forJAK2V617F, 343 for TN, 433 forMPL, and 705 forCALRgenotypes (P < 0 center dot 0001). Duration of CR was shorter inCALR-mutated ET than in the remaining patients (P = 0 center dot 003). InCALR-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% forJAK2V617F,CALR,MPLand TN, respectively;P < 0 center dot 0001). In conclusion, conventional cytoreductive agents are less effective inCALR-mutated ET, highlighting the need for new treatment modalities and redefinition of haematologic targets for patients with this genotype.