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

Nicola Cascavilla, Valerio De Stefano, Fabrizio Pane, Alessandro Pancrazzi, Alessandra Iurlo, Marco Gobbi, Francesca Palandri, Giorgina Specchia, A Marina Liberati, Mariella D'Adda, Gianluca Gaidano, Rajmonda Fjerza, Heinrich Achenbach, Jonathan Smith, Paul Wilde, Alessandro M Vannucchi, Nicola Cascavilla, Valerio De Stefano, Fabrizio Pane, Alessandro Pancrazzi, Alessandra Iurlo, Marco Gobbi, Francesca Palandri, Giorgina Specchia, A Marina Liberati, Mariella D'Adda, Gianluca Gaidano, Rajmonda Fjerza, Heinrich Achenbach, Jonathan Smith, Paul Wilde, Alessandro M Vannucchi

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 (≤600×10(9)/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: JAK2; allele burden; anagrelide; essential thrombocythemia; mutation; treatment response.

Figures

Figure 1
Figure 1
Treatment response comparisons at 12 months for the JAK2-positive and JAK2-negative groups. Notes: (A) Full analysis set; (B) LOCF sensitivity analyses. Abbreviations: CI, confidence interval; LOCF, last observation carried forward; OR, odds ratio.
Figure 2
Figure 2
Treatment response comparisons at 6 months for the JAK2-positive and JAK2-negative groups. Notes: (A) Full analysis set; (B) LOCF sensitivity analyses. Abbreviations: CI, confidence interval; LOCF, last observation carried forward; OR, odds ratio.

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