Expert Shares Strategies for Treating High-Risk ET, PV

When it comes to managing high-risk patients with essential thrombocythemia (ET) or polycythemia vera (PV), John Mascarenhas, MD, starts with risk stratification.

John Mascarenhas, MD

When it comes to managing high-risk patients with essential thrombocythemia (ET) or polycythemia vera (PV), John Mascarenhas, MD, starts with risk stratification, he told colleagues during a "How I Treat" session at the second annual ASH Meeting on Hematologic Malignancies in Chicago.

Mascarenhas, associate professor of medicine, Myeloproliferative Disorders Program, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, began his remarks by reviewing the World Health Organization’s 2016 diagnostic criteria for both ET and PV.1He noted that the PV criteria now include a bone marrow biopsy to make the diagnosis.

When stratifying for risk in both ET and PV, Mascarenhas evaluates 4 key concerns: risk of death, risk of vascular events, risk of progression to post-ET or post-PV myelofibrosis, and risk of progression to acute myeloid leukemia (AML).

Mascarenhas discussed chart review findings from the International Working Group for Myeloproliferative Neoplasms Research and Treatment (IWG-MRT),2which showed that about one-fifth of PV patients died of thrombotic complications, one-fifth died of acute leukemia, and one-fifth of a second malignancy. “These important findings make clear that PV’s natural course is both chronic and progressive, and ends in acute leukemia,” he said.

For Mascarenhas, risk stratification is based primarily on a history of prior thrombosis and age >60 years, which in turn informs the need for cytoreductive therapy. Cardiovascular risk factors also play a role. Low-risk patients are below age 60 and do not have prior thrombosis or cardiovascular risk factors. Intermediate-risk patients are younger and pre-thrombotic but do have cardiovascular risk factors. High-risk patients are older and have a history of thrombosis. “This simple, validated model is best for community use,”3,4he said. “It makes clear that our treatment goals should be to reduce the thrombosis rate and delay disease transformation.”

In general, he has found that many American colleagues are unfamiliar with his preferred European LeukemiaNet (ELN) response criteria for ET and PV.5“The criteria are very specific about what constitutes complete remission, partial remission, no response and progressive disease, which in turns helps us evaluate our strategies,” he said.

Mascarenas urged colleagues to use a hematocrit (HCT) level <45% as the goal of therapy in PV.6&ldquo;That should always be our target because the CYTO-PV Collaborative Group trial found a four-fold reduction in cardiovascular events among patients whose HCTs were strictly controlled,&rdquo; he said.

He also reiterated that hydroxyurea (HU) remains the first choice for first-line therapy for both high-risk ET and PV patients. &ldquo;The data does not confirm the leukemogenic potential of HU, but that idea often sticks in people&rsquo;s minds,&rdquo; he said.

Mascarenhas reviewed the ELN consensus criteria for HU resistance and intolerance in PV, then queried whether they are clinically relevant. Yes, he said, because HU resistance has been shown to lead to increased risk for both death and disease transformation.7

He also noted that ruxolitinib has a role to play for patients with PV who are HU-resistant or -intolerant. &ldquo;Ruxolitinib is the optimal therapy for second-line after HU to address spleen and symptom burden and to control HCT,&rdquo; he said.

For patients with ET who have HU intolerance or resistance, Mascarenhas called anagrelide &ldquo;an appropriate second-line option.&rdquo;

Finally, Mascarenhas looked at interferon-&alpha;2a (IFN-&alpha;) therapy, which he noted has only regional support in the United States. The therapy is currently being studied in a randomized trial of high-risk PV and ET patients who are randomized to either HU or IFN- &alpha;. &ldquo;IFN-&alpha; holds the potential for disease course modification (phase III results are expected soon) and may be best used in younger individuals and during pregnancy,&rdquo; he said (NCT01259856).

However, he also urged colleagues to be attentive to patients&rsquo; complaints of anxiety and depression while on interferon: &ldquo;Interferon is not easy to tolerate, and it can be easy for us to overlook quality-of-life symptoms that often influence patients&rsquo; willingness to continue with a treatment.&rdquo;


  1. Arber DA, Orazi A, Hasserjian R, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia.Blood.2016; 127(20):2391-2405.
  2. Tefferi A, Rumi E, Finazzi G, et al. Survival and prognosis among 1545 patients with contemporary polycythemia vera: an international study.Leukemia.2013;27(9):1874-1881.
  3. Marchioli R, Finazzi G, Landolfi R, et al. Vascular and neoplastic risk in a large cohort of patients with polycythemia vera.J Clin Oncol.2005;23(10:2224-2232.
  4. Barbui T, Barosi G, Birgegard G, et al. Philadelphia-negative classical myeloproliferative neoplasms: critical concepts and management recommendations from European LeukemiaNet.J Clin Oncol.2011;29(6):761-770.
  5. Barosi G, Birgegard G, Finazzi G, et al. Response criteria for essential thrombocythemia and polycythemia vera: result of a European LeukemiaNet consensus conference.Blood.2009;113(20):4829-4833.
  6. Marchioli R, Finazzi G, Specchia G, et al. Cardiovascular events and intensity of treatment in polycythemia vera.N Engl J Med.2013;368(1):22-33.
  7. Alvarez-Larr&aacute;n A, Pereira A, Cervantes F, et al. Assessment and prognostic value of the European LeukemiaNet criteria for clinicohematologic response, resistance, and intolerance to hydroxyurea in polycythemia vera.Blood.2012;119(6):1363-1369.
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