The Treatment Spectrum in Essential Thrombocythemia


Pankit Vachhani, MD, highlights treatment considerations in low- to high-risk essential thrombocythemia and patients resistant or intolerant to hydroxyurea. 

Pankit Vachhani, MD: When I approach treatment for essential thrombocytosis, I keep in mind that there is no single drug or agent that that improves survival. My treatment goals are directed toward the mitigation of the thrombosis risk that these patients have. Also, there is no drug available that slows the progression of essential thrombocytosis to plastic-phase disease or overt myelofibrosis. My general approach to the treatment of essential thrombocytosis is thrombosis risk-adapted management, which largely follows the 4 risk categories found in the revised IPSET [International Prognostic Score for Thrombosis in Essential Thrombocythemia] stratification.

For all my patients, I encourage modification of cardiovascular risk factors. That is of course a key whether you have essential thrombocytosis or not, but especially if you have thrombocytosis that becomes the absolute key. For low-risk patients I suggest a daily aspirin but no cytoreductive therapy for very low-risk or low-risk patients. The caveat is that if patients present with a very high platelet count, let’s say 1.5 million per mm3 or more or they have symptoms, I guide my treatment choice of cytoreductive therapy in those scenarios based on whether they meet certain indication for cytoreductive therapy. That could be identification of new thrombosis, progressive symptoms, or a bleeding tendency. In those patients who present with platelet counts, more than 1.5 million or sometimes even more than 1 million, I routinely check von Willebrand factor profile. If the risk of activity is less than 30% and especially if it is less than 20%, I institute cytoreductive therapy.

In those who have intermediate-risk essential thrombocytosis, I do aspirin and of course modification of cardiovascular risk factors. The use of cytoreductive therapy, typically hydroxyurea, is a decision that I base on other indications for the use of cytoreductive therapies—the ones we just went over. When it comes to high-risk essential thrombocytosis, using an aspirin and modifying cardiovascular risk factors are of course key, but cytoreductive therapy is definitely recommended in this group of patients. The first-line treatment that we use, especially in the United States, is hydroxyurea. This is based on many clinical studies that have investigated hydroxyurea, the first of which was from the 1990s and looked at patients who were at high risk of thrombosis and they were randomized either to hydroxyurea or no myelosuppressive therapy.

A clear thrombosis tree survival was noted in favor of hydroxyurea. Subsequent to that we have the PT-1 study, where patients were randomized to hydroxyurea and aspirin vs anagrelide and aspirin and hydroxyurea arm was favored in terms of thrombosis prevention. That is our first-line treatment of choice when it comes to cytoreductive therapies.

For patients who are resistant or refractory to hydroxyurea use or, for example have an intolerance in the form of adverse events like ulcers or anemia, there are a few other options. One is anagrelide, which is a quinolone inhibitor that reduces the platelet count by inhibiting megakaryocytic differentiation. With anagrelide, the white [blood cell] count, largely speaking, remains unaffected. With regard to anagrelide, remember that there are 2 large studies that have investigated anagrelide. One is the PT-1 study that we just discussed, in which patients were randomized to anagrelide plus aspirin vs Hydrea plus aspirin and the Hydrea arm appeared to be superior. Then there is ANAHYDRET study, a smaller study with the newer definition, the WHO [World Health Organization]–based definition of essential thrombocytosis.

When patients were randomized to Hydrea or anagrelide, aspirin use was not mandatory. And the study was a noninferiority study, and the drugs were found to be similar based on noninferiority study. We typically restrict the use of anagrelide in the second-line setting. Another agent of note is interferon. Interferon has been looked into in essential thrombocytosis for many years. More recently the MPD-RC 112 study randomized patients with polycythemia vera and essential thrombocytosis to interferon or Hydrea, and at least 2 years, with a limited population there were no major clinically useful differences between the 2 arms.

We typically restrict interferon to the relapsed/refractory or intolerant setting for essential thrombocytosis. When we use interferon, we typically use a pegylated form of interferon because the patients find it to be more convenient in that setting.

Options beyond interferon and anagrelide include drugs that may have genome toxicity that and we rarely use. But also ruxolitinib has been studied in the MAGIC trial. Unfortunately, the MAGIC trial did not show any major difference between Hydrea and ruxolitinib. However, those who had symptoms found more resolution of symptoms with ruxolitinib rather than hydroxyurea.

Transcripts edited for clarity.

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