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Impact of JAK2(V617F) mutation status on treatment response to anagrelide in essential thrombocythemia: an observational, hypothesis-generating study

Authors Cascavilla N, De Stefano V, Pane F, Pancrazzi A, Iurlo A, Gobbi M, Palandri F, Specchia G, Liberati AM, D'Adda M, Gaidano G, Fjerza R, Achenbach H, Smith J, Wilde P, Vannucchi AM

Received 19 December 2014

Accepted for publication 24 February 2015

Published 18 May 2015 Volume 2015:9 Pages 2687—2694

DOI https://doi.org/10.2147/DDDT.S79576

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Editor who approved publication: Prof. Dr. Wei Duan


Nicola Cascavilla,1 Valerio De Stefano,2 Fabrizio Pane,3 Alessandro Pancrazzi,4 Alessandra Iurlo,5 Marco Gobbi,6 Francesca Palandri,7 Giorgina Specchia,8 A Marina Liberati,9 Mariella D’Adda,10 Gianluca Gaidano,11 Rajmonda Fjerza,4 Heinrich Achenbach,12 Jonathan Smith,13 Paul Wilde,13 Alessandro M Vannucchi4

1Division of Hematology, Casa Sollievo della Sofferenza Hospital, IRCCS, San Giovanni Rotondo, Italy; 2Institute of Hematology, Catholic University, Rome, Italy; 3Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy; 4Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy; 5Oncohematology Unit, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, Milan, Italy; 6IRCCS AOU San Martino, Genova, Italy; 7Department of Specialistic, Diagnostic and Experimental Medicine, St Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy; 8Unit of Hematology with Transplantation, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy; 9Ospedale Santa Maria, Terni, Italy; 10Division of Hematology, Azienda Ospedaliera Spedali Civili di Brescia, Brescia, Italy; 11Division of Hematology, Department of Translational Medicine, Amedeo Avogadro University of Eastern Piedmont, Novara, Italy; 12Research and Development, Shire GmbH, Eysins, Switzerland; 13Shire Pharmaceutical Development Ltd, Basingstoke, United Kingdom

Abstract: A JAK2(V617F) mutation is found in approximately 55% of patients with essential thrombocythemia (ET), and represents a key World Health Organization diagnostic criterion. This hypothesis-generating study (NCT01352585) explored the impact of JAK2(V617F) mutation status on treatment response to anagrelide in patients with ET who were intolerant/refractory to their current cytoreductive therapy. The primary objective was to compare the proportion of JAK2-positive versus JAK2-negative patients who achieved at least a partial platelet response (≤600×109/L) after anagrelide therapy. Of the 47 patients enrolled, 46 were included in the full analysis set (JAK2-positive, n=22; JAK2-negative, n=24). At 12 months, 35 patients (n=14 and n=21, respectively) had a suitable platelet sample; of these, 74.3% (n=26) achieved at least a partial response. The response rate was higher in JAK2-positive (85.7%, n=12) versus JAK2-negative patients (66.7%, n=14) (odds ratio [OR] 3.00; 95% confidence interval [CI] 0.44, 33.97). By using the last observation carried forward approach in the sensitivity analysis, which considered the imbalance in patients with suitable samples between groups, the overall response rate was 71.7% (n=33/46), with 77.3% (n=17/22) of JAK2-positive and 66.7% (n=16/24) of JAK2-negative patients achieving at least a partial response (OR 1.70; 95% CI 0.39, 8.02). There was no significant change in median allele burden over 12 months in the 12 patients who achieved a response. In conclusion, the overall platelet response rate was high in both JAK2-positive and JAK2-negative patients; however, a larger study would be required to confirm the differences observed according to JAK2(V617F) mutation status.

Keywords: essential thrombocythemia, mutation, JAK2, anagrelide, treatment response, allele burden

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