New Horizons in Treatment for Patients With Polycythemia Vera

bone cancer

Ruben Mesa, MD

The news of a shifting landscape for the diagnosis and treatment of polycythemia vera (PV) is a good thing for patients and practitioners. The altered playing field means refined criteria for diagnosing symptomatic patients, identifying those at highest risk, and an impressive arsenal for treating a disease which carries such heavy symptom burdens.

“Polycythemia vera is a disease that is evolving quite a bit—it really is not the ‘P vera’ of 1995, in which it was just a question of phlebotomy, aspirin, and hydroxyurea,” Ruben A. Mesa, MD, deputy director of the Mayo Clinic Cancer Center in Phoenix, Arizona, professor and chair of the Division of Hematology & Medical Oncology, told attendees at a session on hematologic malignancies which opened the 33rd Annual Chemotherapy Foundation Symposium.

One vital way where understanding of the disease has advanced is the development of more rigorous diagnostic criteria for PV, he said. Mesa noted that many patients will show signs of PV but may not meet thresholds set by the World Health Organization (WHO) in its 2008 guidelines. Guidelines WHO is expected to revise in 2016, with revisions such as a lower hemoglobin threshold for unexplained erythrocytosis.

“The criteria are becoming more sensitive,” Mesa noted with the addition that even that doesn't tell the whole story considering PV carries a heavy symptom burden, including vascular events, cytopenias, and splenomegaly, along with a risk of progression to myelofibrosis or acute leukemia.  

“Our understanding of risk has evolved as well,” continued Mesa. Key factors in assessing prognosis and progression risk include age, leukocytosis, and prior thrombotic events.  

Mesa said that goals of PV treatment include complete remission, a decrease in symptoms, and “near-normal” blood counts and bone marrow. European LeukemiaNET guidelines are currently used to inform PV management; Mesa added, however, that he is part of a group that is currently working to develop NCCN guidelines for myeloproliferative neoplasms.    

Current management of all PV patients includes maintaining hematocrit levels <45% in men and <42% in women, though some patients may benefit from a lower threshold based on their symptom burden and history, said Mesa. In addition, low-dose (&le;100 mg) aspirin is recommended for those who not allergic or intolerant, along with aggressive control of cardiovascular risk factors. &nbsp;

Mesa said the use of cytroreduction for treatment of PV is also evolving in important ways. Though hydroxyurea remains the default standard of care, limitations of this treatment have generated significant interest in new agents. &nbsp;

Phase III global programs are underway examining pegylated interferon alpha (PEG-IFN &alpha;) as frontline therapy in high-risk PV patients. The MD-RC 112 study (NCT01259856) will compare PEG-IFN-2a (PEGASYS) with hydroxyurea and aspirin in patients with essential thrombocythemia or PV and is currently recruiting participants. Another trial (NCT01949805) is comparing Peg-P-IFN-alpha-2b&nbsp;(AOP2014) with hydroxyurea in patients with high-risk PV. Mesa said that results for the latter were reported recently, and the agent produced durable responses (Am J Hematol. 2015;90(4):288-294). &nbsp;&nbsp;

Because JAK2 driver mutations are commonly associated with PV, JAK inhibitors represent another area of interest, among them, ruxolitinib. Mesa cited findings from the RESPONSE study showing that the oral JAK1/JAK2 inhibitor was superior to best alternative therapy (BAT) in such areas as improving blood cell counts and reducing the phlebotomy procedures in patients with difficult PV, a significant unmet need. Ruxolitinib demonstrated durable responses and eased symptom burden (N Engl J Med.2015; 72[5]:426-435). &nbsp;&nbsp;

Additionally, Mesa reported, at an 80-week analysis, rates of thromboembolic adverse events per 100 patient years of exposure were 1.8 in the ruxolitinib arm versus 8.2 in the BAT arm, marking a &ldquo;very favorable trend for the decrease in these events,&rdquo; said Mesa.