Data have been presented in part at the 2012 Annual Meeting of the American Society of Hematology; December 8-11, 2012; Atlanta, GA.
A phase 2 study of ruxolitinib, an oral JAK1 and JAK2 inhibitor, in patients with advanced polycythemia vera who are refractory or intolerant to hydroxyurea
Article first published online: 30 OCT 2013
© 2013 The Authors published by Wiley Periodicals, Inc. on behalf of American Cancer Society.
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
Volume 120, Issue 4, pages 513–520, 15 February 2014
How to Cite
Verstovsek, S., Passamonti, F., Rambaldi, A., Barosi, G., Rosen, P. J., Rumi, E., Gattoni, E., Pieri, L., Guglielmelli, P., Elena, C., He, S., Contel, N., Mookerjee, B., Sandor, V., Cazzola, M., Kantarjian, H. M., Barbui, T. and Vannucchi, A. M. (2014), A phase 2 study of ruxolitinib, an oral JAK1 and JAK2 inhibitor, in patients with advanced polycythemia vera who are refractory or intolerant to hydroxyurea. Cancer, 120: 513–520. doi: 10.1002/cncr.28441
We thank Kris Vaddi, PhD, for biomarker data review; Kevin Hou, PhD, for biostatistical support; William Garrett, MBA, for study management; and Hema Gowda, PharmD, for medical writing assistance (all from Incyte Corporation). Granulocyte activation studies were performed at the Fondazione IRCCS Policlinico San Matteo and the University of Pavia in Pavia, Italy. Studies of microRNA expression were conducted at the Section of Hematology at the University of Florence in Florence, Italy, with the acknowledged contribution of Rossella Manfredini of the University of Modena and Reggio Emilia in Modena, Italy.
- Issue published online: 4 FEB 2014
- Article first published online: 30 OCT 2013
- Manuscript Accepted: 17 SEP 2013
- Manuscript Revised: 4 SEP 2013
- Manuscript Received: 21 AUG 2013
- polycythemia vera;
- myeloproliferative neoplasm;
- Janus kinase (JAK) inhibitor;
- phase 2
Polycythemia vera (PV) is a myeloproliferative neoplasm associated with somatic gain-of-function mutations of Janus kinase-2 (JAK2). Therapeutic options are limited in patients with advanced disease. Ruxolitinib, an oral JAK1/JAK2 inhibitor, is active in preclinical models of PV. The long-term efficacy and safety of ruxolitinib in patients with advanced PV who are refractory or intolerant to hydroxyurea were studied in a phase 2 trial.
Response was assessed using modified European LeukemiaNet criteria, which included a reduction in hematocrit to < 45% without phlebotomy, resolution of palpable splenomegaly, normalization of white blood cell and platelet counts, and reduction in PV-associated symptoms.
Thirty-four patients received ruxolitinib for a median of 152 weeks (range, 31 weeks-177 weeks) or 35.0 months (range, 7.1 months-40.7 months). Hematocrit < 45% without phlebotomy was achieved in 97% of patients by week 24. Only 1 patient required a phlebotomy after week 4. Among patients with palpable splenomegaly at baseline, 44% and 63%, respectively, achieved nonpalpable spleen measurements at weeks 24 and 144. Clinically meaningful improvements in pruritus, night sweats, and bone pain were observed within 4 weeks of the initiation of therapy and maintained with continued treatment. Ruxolitinib treatment also reduced elevated levels of inflammatory cytokines and granulocyte activation. Thrombocytopenia and anemia were the most common adverse events. Thrombocytopenia of ≥ grade 3 or anemia of ≥ grade 3 (according to National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0) occurred in 3 patients each (9%) (1 patient had both) and were managed with dose modification.
Ruxolitinib was generally well tolerated and provided rapid and durable clinical benefits in patients with advanced PV who were refractory or intolerant to hydroxyurea. Cancer 2014;120:513–20. © 2013 The Authors published by Wiley Periodicals, Inc. on behalf of American Cancer Society.