The results of phase III study evaluating a JAK 1/2 inhibitor for the treatment of polycythemia vera were presented at the 50th Annual Meeting of the American Society of Clinical Oncology ( ASCO ).
Ruxolitinib ( Jakavi ) has significantly improved hematocrit control without the need for phlebotomy ( a procedure to remove blood from the body to reduce the concentration of red blood cells ) and reduced spleen size in patients with polycythemia vera who are resistant to or intolerant of Hydroxyurea.
In the RESPONSE trial, patients treated with Ruxolitinib showed better disease control, including controlled hematocrit levels without the need for phlebotomy, reduced spleen size and improved symptom management compared to current therapies.
At week 32 of the study, 77% of patients randomized to Ruxolitinib achieved one or both components of the composite endpoint of hematocrit control ( volume percentage of red blood cells in whole blood ) or spleen size reduction in comparison with 20% of patients randomized to best available therapy.
A significantly greater proportion of patients achieved the composite primary endpoint when treated with Ruxolitinib compared to best available therapy ( 21% compared to 1%, respectively; p less than 0.0001 ), and 91% of these patients treated with Ruxolitinib maintained their response at week 48.
In the study, a 50% or more improvement in polycythemia vera-related symptoms was seen in 49% of Ruxolitinib-treated patients compared to 5% of patients treated with best available therapy.
Patients treated with Ruxolitinib also experienced a reduction in night sweats and itchiness ( approximately 99% and 95%, respectively ).
In addition, a greater proportion of patients on the Ruxolitinib treatment arm achieved complete hematologic response as defined by the modified 2009 European LeukemiaNet ( ELN ) criteria, a key secondary endpoint, when compared to the best available therapy arm ( 24% compared to 9%, respectively; p=0.003 ).
Ruxolitinib was well tolerated and adverse events were consistent with those previously seen in Ruxolitinib studies in polycythemia vera and myelofibrosis.
Within the first 32 weeks of treatment, grade 3 or 4 hematologic adverse reactions in the Ruxolitinib treatment arm were anemia ( 1.8% ) and thrombocytopenia ( 5.5% ), and fewer patients treated with Ruxolitinib experienced thromboembolic events when compared to those who received best available therapy ( 1 patient compared to 6 patients, respectively ).
The most common non-hematologic adverse reactions were headache, diarrhea and fatigue, which were mainly grade 1 or 2. Additionally, 3.6% of patients randomized to the Ruxolitinib treatment arm discontinued treatment due to adverse reactions compared to 1.8% on the best available therapy arm.
RESPONSE is a global, randomized, open-label study conducted at 109 sites. 222 patients with polycythemia vera resistant to or intolerant of Hydroxyurea were randomized 1:1 to receive either Ruxolitinib ( starting dose of 10 mg twice-daily ) or best available therapy, which was defined as investigator selected monotherapy or observation only.
Ruxolitinib dose was adjusted as needed throughout the study.
The primary endpoint of the study was the proportion of patients whose hematocrit was controlled without phlebotomy from week 8 through 32 and whose spleen volume was reduced by 35% or more from baseline as assessed by imaging at 32 weeks.
In addition, efficacy was further assessed using two key secondary endpoints: durable primary response and complete hematological remission. Other endpoints include safety, symptom improvement ( as measured by the MPN-SAF 14-item total symptom score ) and quality of life.
Polycythemia vera is a chronic, incurable blood cancer associated with an overproduction of blood cells in the bone marrow that affects roughly one to three people per 100,000 globally. It is typically characterized by an elevated hematocrit, the volume percentage of red blood cells in whole blood, which can lead to a thickening of the blood and an increased risk of blood clots. This can cause serious cardiovascular complications, such as stroke and myocardial infarction, resulting in increased morbidity and mortality.
Phlebotomy, a procedure to remove blood from the body to reduce the concentration of red blood cells, is commonly used to maintain a normal hematocrit level.
Additionally, patients with polycythemia vera often have enlarged spleen and numerous debilitating symptoms that significantly affect their daily life.
A proportion of patients become intolerant or resistant to currently available therapies. In fact, approximately 25% of polycythemia vera patients become resistant to or intolerant of Hydroxyurea treatment, which results in inadequate disease control and an increased risk of progression.
Ruxolitinib is an oral inhibitor of the JAK 1 and JAK 2 tyrosine kinases and was approved by the European Commission in August 2012 for the treatment of disease-related splenomegaly or symptoms in adult patients with primary myelofibrosis ( also known as chronic idiopathic myelofibrosis ), post-polycythemia vera myelofibrosis or post-essential thrombocythemia myelofibrosis. ( Xagena )
Source: Novartis, 2014