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Ruxolitinib is approved by the FDA for the treatment of patients with PV who have had an inadequate response to or are intolerant of hydroxyurea.99 Further research will be important for identifying other populations of patients with PV who may benefit from treatment with ruxolitinib. RESPONSE 2 ( identifier: NCT02038036) is an ongoing, randomized, open-label, Phase IIIb clinical trial designed to evaluate the efficacy and safety of ruxolitinib compared with the best available therapy in patients with PV without splenomegaly who are resistant to or intolerant of hydroxyurea and require phlebotomy.116 The primary endpoint is achievement of hematocrit control at Week 16 that is maintained through Week 28, together with no phlebotomy eligibility from Weeks 4 to 28.116 Patients who are randomized to the best available therapy and do not meet the primary endpoint are allowed to cross over to ruxolitinib at or after Week 28.116 Safety and durability of response will be evaluated through Week 52.116


Ruxolitinib is the only approved treatment option designed to target the constitutively active JAK/STAT signaling pathway in patients with PV. Ruxolitinib improves hematocrit control without phlebotomy, improves blood cell counts, and reduces the enlarged spleen size.22,107 Accumulating evidence suggests that ruxolitinib may also ameliorate PV-related symptoms in patients who are resistant to and/or intolerant of hydroxyurea. Most adverse events were grade 1 or 2, and 82.7% of patients continued on treatment for ≥80 weeks in Phase III RESPONSE trial. Nonmelanoma skin cancer has been observed with ruxolitinib treatment, and periodic skin examinations should be performed. Herpes zoster infection rates (all grade 1 or 2) were higher with ruxolitinib compared with the best available therapy in the RESPONSE trial,22 and patients receiving ruxolitinib should be advised about the early signs and symptoms of infection and instructed to seek treatment as early as possible if suspected. Rates of disease transformation to MF and AML observed with ruxolitinib22 are similar to those previously published in similar patient populations with PV.84,115

Collectively, clinical trial data indicate that ruxolitinib is an effective treatment option for many patients with PV who are resistant to and/or intolerant of hydroxyurea. Furthermore, the potential benefits of ruxolitinib are unique when compared with the traditional treatment options because ruxolitinib may alleviate the PV-related symptom burden and improve the QoL. Updated treatment guidelines will be important for educating physicians about using ruxolitinib for the treatment of patients with PV.


Writing assistance was provided by Phuong Tran, PharmD, MBA (Complete Healthcare Communications, LLC, Chadds Ford, PA, USA, an ICON plc company), whose work was funded by Incyte Corporation, Wilmington, DE, USA.


KV is an employee of Incyte Corporation. SV participated in advisory boards and received research funding from Incyte Corporation. JJK served as a consultant for Incyte Corporation and Novartis and received a travel grant and research funding paid by Novartis to Hôpital Saint-Louis. The authors report no other conflicts of interest in this work.

Kris Vaddi,1 Srdan Verstovsek,2 Jean-Jacques Kiladjian3

1Drug Discovery, Incyte Corporation, Wilmington, DE, 2Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; 3Clinical Investigations Center, Hôpital Saint-Louis et Université Paris Diderot, Paris, France 


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Source: Blood and Lymphatic Cancer: Targets and Therapy
Originally published May 12, 2016.