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Ruxolitinib decreased hematocrit, spleen volume in hydroxyurea-resistant polycythemia vera
CHICAGO — Ruxolitinib achieved superior disease control compared with best available therapy in patients with polycythemia vera who were resistant to or intolerant of hydroxyurea, according to results of the phase 3 RESPONSE trial presented at the ASCO Annual Meeting.
Ruxolitinib (Jakafi, Incyte), a JAK1 and JAK2 inhibitor, significantly improved hematocrit control without the need for phlebotomy, results showed. It also was more effective with regard to reduction of spleen volume, normalization of blood cell count and decrease in polycythemia vera-related systemic symptoms.
The goal of therapy usually is to control hematocrit, or to decrease the hematocrit to 45%, because it has been shown before in many studies that significant decreases of hematocrit decreases the risk for cardiovascular death and major thrombotic events, Srdan Verstovsek, MD, PhD, professor in the department of leukemia of The University of Texas MD Anderson Cancer Center and a HemOnc Today Editorial Board member, said during a presentation.
“Hydroxyurea is established first-line cytoreductive therapy for polycythemia vera, but it does not work in all patients,” Verstovsek told HemOnc Today. “Second-line therapies are limited in efficacy and/or cause toxicity.”
A small phase 2 study evaluated ruxolitinib in previously treated patients with refractory polycythemia vera. Results showed the drug was effective for controlling hematocrit, as well as for improving the spleen, symptoms and overall blood cell count, Verstovsek said.
The current analysis included 222 patients with splenomegaly ˃450 cm3 who had hydroxyurea-resistant/intolerant polycythemia vera.
Verstovsek and colleagues randomly assigned 110 patients to 10 mg twice daily ruxolitinib. The other 112 patients were assigned best available therapy, which included hydroxyurea, interferon, several other therapies or observation.
Median treatment exposure was longer in the ruxolitinib arm (81 weeks vs. 34 weeks). Most patients (96%) in the best available therapy arm discontinued treatment, including 96 patients who crossed over to the ruxolitinib arm after week 32. Seventeen patients (15%) discontinued treatment with ruxolitinib.
Overall, a significantly higher number of patients assigned ruxolitinib achieved the primary endpoint of both hematocrit control without phlebotomy and ≥35% reduction in spleen volume (21% vs. 1%; P˂.0001).
Ninety-one percent of patients assigned ruxolitinib had ongoing responses at week 48.
Most patients assigned ruxolitinib (77%) achieved at least one component of the primary endpoint. More patients in the ruxolitinib arm achieved hematocrit control without phlebotomy (60% vs. 20%), and a higher percentage achieved ≥35% reduction in spleen volume (38% vs. 1%).
The incidence of phlebotomy was three times higher in the best available therapy arm (62.4% vs. 19.8%).
Researchers observed complete hematologic response — defined as continuous hematocrit below 45%, as well as normal blood cells and platelets counts — in 24% of patients assigned ruxolitinib vs. 9% of those assigned the best available therapy (P=.003).
More patients assigned ruxolitinib also demonstrated ≥50% improvements in the Myeloproliferative Neoplasm Symptom Assessment Form 14-item total symptom score at week 32 (49% vs. 5%).
Grade 3 to grade 4 anemia (1.8% vs. 0%) and thrombocytopenia (5.5% vs. 3.6%) occurred more frequently in the ruxolitinib arm in the first 32 weeks. Thromboembolic events occurred in six patients assigned best available therapy and one patient assigned ruxolitinib.
“This demonstrates that ruxolitinib may be a valuable new therapeutic option in this population of previously treated, hydroxyurea-refractory patients with uncontrolled polycythemia vera,” Verstovsek said.
For more information:
Verstovsek S. Abstract #7026. Presented at: ASCO Annual Meeting; May 30-June 3, 2014; Chicago.
Disclosure: Verstovsek reports research funding from Incyte. Other researchers report research funding or honoraria from, consultant/advisory roles or employment/leadership positions with, and stock ownership in Incyte and Novartis.
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