Lead PERSIST-1 author Ruben A. Mesa, MD, deputy director of the Mayo Clinic Cancer Center in Scottsdale, Arizona, discussed the trial's results and pacritinib's potential to change the treatment paradigm for patients with myelofibrosis.
Ruben A. Mesa, MD
There are limited treatment options for myelofibrosis, especially for patients with low platelet levels. Ruxolitinib (Jakafi) was approved in 2011 for patients with intermediate- or high-risk myelofibrosis, but those with platelet levels <50,000/μL are not eligible for the therapy.
The PERSIST-1 study, which investigated pacritinib daily versus physician’s choice of best available therapy excluding prior ruxolitinib, was the first phase III study of its kind to open enrollment to patients with myelofibrosis with all platelet levels. In the study, which was presented at the 2015 ASCO Annual Meeting, hydroxycarbamide (55.7%) and a watch-and-wait strategy (25.5%) were the most prevalent options used in the control arm as best available therapy.
Of the 327 patients enrolled, 32% had platelet levels <100,000/μL and 15% had platelet levels <50,000/μL. Pacritinib showed benefit among patients regardless of their platelet levels.
The primary endpoint of spleen volume reduction ≥35% was achieved not only in the intent-to-treat (ITT) population, but also among all evaluable patients.
In the evaluable patient population, 25% of patients who received pacritinib (n = 168) reached the spleen volume reduction threshold, versus 5.9% of the best available therapy arm (n = 85; P = .0001). The rate of patients with <50,000/μL platelets who achieved spleen volume reduction ≥35% was 22.9% and 33.3% for the ITT and evaluable populations, respectively. For those patients with baseline thrombocytopenia and <100,000/μL platelets, 16.7% and 23.5% achieved spleen volume reduction ≥35% in the ITT population and evaluable groups, respectively.
In an interview with OncLive, lead PERSIST-1 author Ruben A. Mesa, MD, deputy director of the Mayo Clinic Cancer Center in Scottsdale, Arizona, discussed the trial’s results and pacritinib’s potential to change the treatment paradigm for patients with myelofibrosis.
OncLive: What were the most significant findings from the PERSIST-1 study?
Dr Mesa: Myelofibrosis is chronic myeloproliferative neoplasms that afflict patients with significant splenomegaly symptoms and low blood counts, and can potentially lead to mortality from the disease. The PERSIST-1 study is a randomized study of pacritinib versus best alternative therapy. Pacritinib is a JAK2/FLT3 inhibitor, which, in early studies, demonstrated the ability to improve splenomegaly symptoms in these patients and also improve low blood counts. This is a unique factor for the drug. The trial included patients who had intermediate- and high-risk myelofibrosis, and uniquely did not exclude patients who had significant thrombocytopenia when they entered the study. Prior to this, there had been no phase III study done in this space on patients with platelet counts less than 100,000.
What we found, which we presented at the 2015 ASCO Annual Meeting, was that pacritinib was superior to best alternative therapy for all of our main endpoints. The first endpoint was a reduction in spleen size, which was significant in all the groups, but particularly in the individuals with thrombocytopenia. The second endpoint was an improvement in myelofibrosis symptoms. This was true when we looked at individual symptoms as well as in aggregate by a total symptom score. We also identified that platelets sometimes increase in patients as a result of pacritinib, with 35% of patients having an improvement in their platelet count. Finally, 25% of patients who entered the study red blood cell transfusion dependent became transfusion independent.
What is the prevalence of patients with myelofibrosis and low platelet counts for whom this therapy is intended?
We estimate that in the United States, there are probably around 20,000 patients with myelofibrosis. About one-third of these individuals have significant thrombocytopenia. We also recognize that when patients have the disease for a longer period of time, thrombocytopenia becomes more prevalent.
Can you compare the characteristics and optimal patient populations for pacritinib and ruxolitinib, which are both JAK inhibitors?
The study was pacritinib versus best alternative therapy and ruxolitinib was not directly compared. This was in part because ruxolitinib was not indicated for patients with platelet counts of fewer than 100,000 when the trial started, and is not indicated for patients with platelet counts under 50,000 even as we stand now. It is difficult to judge two different sets of data done in parallel without a direct head-to-head comparison. However, what I can say, is that there are significant benefits in splenomegaly symptoms demonstrated in both drugs’ phase III studies. The PERSIST-1 study, similar to the COMFORT study done in ruxolitinib, examined JAK2-naïve patients; there was significant benefit.
Would the availability of a drug for patients with low platelets change the treatment paradigm?
I think it really helps to complete the paradigm. At the current time, these individuals really have no alternative options. We see that by looking at what was selected as best alternative therapy. There was no indicative therapy, so it ended up being a mixture of things, which ranged from supportive care alone to a range of other medicines that were truly not effective.