Ruxolitinib reduces JAK2 p.V617F allele burden in patients with polycythemia vera enrolled in the RESPONSE study

Annals of Hematology - Tập 96 - Trang 1113-1120 - 2017
Alessandro Maria Vannucchi1,2, Srdan Verstovsek3, Paola Guglielmelli1,2, Martin Griesshammer4,5, Timothy C. Burn6, Ahmad Naim6, Dilan Paranagama6, Mahtab Marker7, Brian Gadbaw7, Jean-Jacques Kiladjian8
1Center for Research and Innovation of Myeloproliferative Neoplasms (CRIMM), AOU Careggi, Florence, Italy
2Laboratorio Congiunto and Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
3Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, USA
4University Clinic for Hematology, Oncology, Hemostaseology and Palliative Care, Johannes Wesling Medical Center, Minden, Germany
5UKRUB, University of Bochum, Bochum, Germany
6Incyte Corporation, Wilmington, USA.
7Novartis Pharmaceuticals Corporation, East Hanover, USA
8Centre d’Investigations Cliniques (INSERM CIC 1427), Hôpital Saint-Louis, Université Paris Diderot, Paris, France

Tóm tắt

In patients with polycythemia vera (PV), an elevated JAK2 p.V617F allele burden is associated with indicators of more severe disease (e.g., leukocytosis, splenomegaly, and increased thrombosis risk); however, correlations between allele burden reductions and clinical benefit in patients with PV have not been extensively evaluated in a randomized trial. This exploratory analysis from the multicenter, open-label, phase 3 Randomized Study of Efficacy and Safety in Polycythemia Vera With JAK Inhibitor INCB018424 Versus Best Supportive Care trial evaluated the long-term effect of ruxolitinib treatment on JAK2 p.V617F allele burden in patients with PV. Evaluable JAK2 p.V617F-positive patients randomized to ruxolitinib (n = 107) or best available therapy (BAT) who crossed over to ruxolitinib at week 32 (n = 97) had consistent JAK2 p.V617F allele burden reductions throughout the study. At all time points measured (up to weeks 208 [ruxolitinib-randomized] and 176 [ruxolitinib crossover]), mean changes from baseline over time in JAK2 p.V617F allele burden ranged from −12.2 to −40.0% (ruxolitinib-randomized) and −6.3 to −17.8% (ruxolitinib crossover). Complete or partial molecular response was observed in 3 patients (ruxolitinib-randomized, n = 2; ruxolitinib crossover, n = 1) and 54 patients (ruxolitinib-randomized, n = 33; ruxolitinib crossover, n = 20; BAT, n = 1), respectively. Among patients treated with interferon as BAT (n = 13), the mean maximal reduction in allele burden from baseline was 25.6% after crossover to ruxolitinib versus 6.6% before crossover. Collectively, the data from this exploratory analysis suggest that ruxolitinib treatment for up to 4 years provides progressive reductions in JAK2 p.V617F allele burden in patients with PV who are resistant to or intolerant of hydroxyurea. The relationship between allele burden changes and clinical outcomes in patients with PV remains unclear.

Tài liệu tham khảo

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