Unmet clinical needs in the management of CALR-mutated essential thrombocythaemia: a consensus-based proposal from the European LeukemiaNet

Recommendations regarding management of essential thrombocythaemia rely on studi e s done before the discovery of the CALR mutation. On May 20, 2020, the Europ e a n LeukemiaNet annual meeting was held with the goal to identify unmet clin i c a l needs in myeloproliferative neoplasms. Because patients with a CALR mutation have specific clinica l characteristics, treatment of CALR-mutated essential thrombocythaemia was considered an unmet clinical need by the Europ e a n LeukemiaNet. The elaboration of a consensus document with recommendations according to current evidence was proposed as a solution for resolving uncertainties in the treatment of CALR-mutated essential thrombocythaemia. A steering committee comprising f o u r Europ e a n LeukemiaNet members was t h e n formed and a panel of ten experts in the field was recruited. T h e experts proposed 51 potential unmet clinical needs in the management of CALR-mutated essential thrombocythaemia and were as k e d to score the relevance of each topic. Those topics that obtained the highest scores as relevant unmet clinical needs were identified, including antiplat e l e t therapy in patients at low risk, definition of extreme thrombocytosis and its management in patients at low risk, indications of cytoreduction and tar g e t s of therapy, first-line treatment of choice in young patients (<60 years), and management of pregnancy. After the steering committee revised the available evidence for each topic, a consensus on management and proposal for improving knowledge was achieved by use of an email-based, two round, Delphi approach. Consensus was achie v e d when 90% of the panellists agreed with a statement and included 14 recommendations and six solution proposals. Key recommendations included careful observation for asymptomatic patients with classical, low-risk, CALR-mutated essential thrombocythaemia without cardiovascular risk factors; caution in the use of antiplatelet therapy for symptomatic patients at low risk with plat e l e t counts of 1000-1500 x 109 platelets per L, in such cases cytoreduction is an adequate option, especially if adquired Von Willebrand disease is present; cytoreduction is recommended for extreme thrombocytosis (plat e l e t count >1500 x 109 platelets per L) with pegylated interfe r o n alfa being the preferred option for younger patients; both hydroxycarbamide and anagrelide might be given to patients ineligible for pegylated interferon alfa; and treatment algorithms for patients with high-risk pregnancies should not be changed according to genotype. The European LeukemiaNet proposes to use these recommendations in the routine management of patients wit h CALR-mutated essential thrombocythaemia, and designing new clinica l studies in this field might be useful.