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 studies done before the discovery of the CALR mutation. On May 20, 2020, the European LeukemiaNet annual meeting was held with the goal to identify unmet clinical needs in myeloproliferative neoplasms. Because patients with a CALR mutation have specific clinical characteristics, treatment of CALR-mutated essential thrombocythaemia was considered an unmet clinical need by the European 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 four European LeukemiaNet members was then formed and a panel of ten experts in the field was recruited. The experts proposed 51 potential unmet clinical needs in the management of CALR-mutated essential thrombocythaemia and were asked to score the relevance of each topic. Those topics that obtained the highest scores as relevant unmet clinical needs were identified, including antiplatelet therapy in patients at low risk, definition of extreme thrombocytosis and its management in patients at low risk, indications of cytoreduction and targets 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 achieved 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 platelet counts of 1000-1500 × 10

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Declaration of interests AA-L participated in data safety monitoring boards and advisory boards and has received speaker and consulting fees from Novartis, AOP Orphan, and Celgene. CH had grants or contracts with payment to her institution from Novartis, Celgene, and Constellation, consulting fees from Keros, Galecto, and Roche, speaker fees from Novartis, Celgene, CTI BioPharma, Gilead, Jannsen, Promedior, and Geron, and participated on a data safety monitoring board and advisory board for Roche and Galecto. ER received speaker fees from Novartis and participated in the Abbvie advisory board. FP received speaker fees from Novartis, AOP, and Celgene. JCI received speaker fees from Novartis. J-JK received consulting fees from Abbvie and Novartis, speaker fees from AOP Orphan, Novartis, and Bristol Myers Squibb (BMS), and participated in advisory boards for Incyte. JN received grants from MPN Research Foundation, Alborada Trust, and Rosetrees Trust, and speaker fees from Jazz Pharmaceutical. MG received consulting and speaker fees, payment for expert testimony, support for attending meetings, and participated in data safety monitoring board and advisory board from AOP, Novartis, Celgene, BMS, Amgen, and AstraZeneca. RM received grants from Celgene, Incyte, Abbvie, Samus, Genotech, Promedior, and CTI BioPharma, consulting fees from Novartis, Sierra Onc, LaJolla, and Pharma. SK received grants from AOP, Janssen, and Novartis, consulting fees from Pfizer, CTI BioPharma, Baxalta, Sanofi, Novartis, BMS–Celgene, Incyte, Shire, Roche, AOP, and Janssen, speaker fees from Pfizer, CTI, Baxalta, Sanofi, Novartis, BMS–Celgene, Incyte, Shire, Roche, AOP, and Janssen, support from attending meetings from Pfizer, CTI BioPharma, Baxalta, Sanofi, Novartis, BMS–Celgene, Incyte, Shire, AOP, Janssen, Alexion, and Geron, patents planned, issued, or pending from Rheinisch-Westfälische Technische Hochschule Aachen, and leadership role in Deutsche Gesellschaft für Hämatologie und Medizinische Onkologie. All other authors have no competing interests.