Cytoreductive therapies showed less efficacy in patients with CALR-mutated (CALRm) essential thrombocythemia (ET) compared with other forms of ET, according to the results of a study published in the British Journal of Haematology.

Affecting nearly 20% of patients with ET, CALR mutations are the second most common genetic alterations in this patient group. Patients with these mutations are typically younger, have higher platelet counts, and are at lower risk for thrombosis.

Current guidelines have established that cytoreductive treatment is recommended for patients with ET who are at high risk for thrombosis, patients with extreme thrombocytosis, or patients with persistent postsurgical microvascular symptoms despite antiplatelet therapy.

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“However, given the symptomatic burden, haematologic profile and risk of thrombosis and bleeding may depend on the disease genotypes, the need for cytoreductive treatment could also vary across genotypes,” the authors of the study noted.

A team of investigators conducted a study in association with the prospective Spanish Registry of Essential Thrombocythaemia to characterize the indications and outcomes of cytoreductive treatment in patients with ET who were CALR-positive.

A total of 1446 patients with ET were evaluated for use of cytoreduction and responses to treatment, and with respect to genotypes related to ET; 276 were carriers for a CALR mutation (CALRm).

Cytoreductive agents were given to 1104 (76%) patients, with hydroxycarbamide (977 patients) and anagrelide (113 patients) being the most common agents.

Compared with other ET genotypes, including MPL-mutated (MPLm), JAK2V617F, and triple-negative (TN), low-risk patients with CALRm ET showed a significantly shorter time from diagnosis to initiation of cytoreductive treatment (P <.0001). The median time to initiating cytoreduction was 2.8 years with the CALRm genotype, 3.2 years with an MPLm genotype, 7.4 years with the JAK2V617F genotype, and 12.5 years for patients with TN ET.

The 12-month estimated cumulative rate of complete hematological response was 40% for patients with CALRm, 67% for patients with JAK2V617F ET, 51% for those with TN ET, and 38% for patients with MPLm ET. The duration of CR for patients with CALRm ET was significantly shorter than duration for the rest of the patient population (P =.003).

Additionally, the median time to CR was significantly longer with CALRm ET (705 days) than with other genotypes (P <.0001). For the JAK2V617F genotype the median time to CR was 192, with TN ET it was 343 days, and with MPLmET it was 433 days.

Hydroxycarbamide and anagrelide showed similar rates of efficacy but the 5-year probability of resistance or intolerance to hydroxycarbamide was relatively high with CALRm ET (23%). This probability was 5% with JAK2V617F ET, 15% with TN ET, and 27% with MPLmET.

“In conclusion, patients with CALRm ET have specific requirements for cytoreductive treatment,” the study investigators wrote. Because typical cytoreductive therapies are less efficacious in this patient group than in others with ET, the investigators stressed the need for new therapy approaches to treat ET with this genotype.


Alvarez-Larrán A, Angona A, Andrade-Campos M, et al. Cytoreductive treatment in patients with CALR-mutated essential thrombocythaemia: a study comparing indications and efficacy among genotypes from the Spanish Registry of Essential Thrombocythaemia. Br J Haematol. Published online August 3, 2020. doi:10.1111/bjh.16988