Defining Uncontrolled Polycythemia Vera


Jamile M. Shammo, MD:Hydrea is probably the most commonly utilized cytoreductive therapy for patients who have polycythemia vera. But I think most of us realize that a group of patients do not get benefits from this medication either at the beginning, which fortunately is a very small proportion of patients, or later on as they continue living with PV and receiving Hydrea. So, I think it’s important for us as physicians to monitor those patients. And the fact is that there are certain criteria for Hydrea resistance and intolerance. These were put together by an expert panel. Physicians, who have taken care of large number of people who have MPNs, do realize that there’s a need for optimization of those parameters and perhaps more of a concrete definition as to what is resistance and intolerance.

But I think that most of us would agree that intolerance to Hydrea is something that we’ve all seen and it’s relatively easier to identify if you have someone who develops metalogical toxicity with the low neutrophil count at the initiation of therapy, or anemia, or obviously mucocutaneous manifestations, mouth ulcers, or skin ulcers—although skin ulcers happen later on in the course. I haven’t really seen it early on in therapy. That would be clearly a definition of intolerance. And we’ve all dealt with it, and fortunately, you require to hold the drug and then deal with the consequences of this—think of an alternative basically.

Now resistance on the other hand requires that people actually are aware of what this definition means. What is resistance? Resistance means that you treat patients with at least 3 months of Hydrea, at 2 g or the highest possible dose, and you still continue to have signs of active disease. So, what is that exactly? Well, that’s continuation of requirements for phlebotomy, lack of hematological responses, and continuing to have symptoms related to splenomegaly, constitutional symptoms, and, therefore, you can deem the patient as resistant to the drug.

In the paper that had assessed the likelihood of this developing, it appears as though this could develop later on in the course of therapy like I’d already stated. But it also means that you have to have hematologists that are aware of the criteria, and, look to see how their patient is doing on those agents. So, first and foremost, it’s familiarity with the criteria.

There are several options for treating patients who have polycythemia vera. You have a low- dose patient, perhaps phlebotomy, and a low-dose aspirin is reasonable. If you have a patient who has high-risk disease and you need cytoreduction, there are several options. Hydrea is one of the most commonly utilized. You may utilize it in conjunction with phlebotomy, but at some point, those patients should become phlebotomy-free. Alternatively, interferon is the other agent that people utilize. I have utilized it for young women who are of child-bearing age and they are interested in having a family—hence Hydrea is not an option—so then interferon is reasonable. And obviously, there are clinical trials comparing and contrasting the 2 agents upfront and we have to wait for the data.

The other option is anagrelide. I have not utilized anagrelide for patients with PV. Anagrelide is an option, but I don’t think we utilize it; it’s a personal choice. That’s all I can say.

Finally, for the patient population that has demonstrated resistance or intolerance, there’s an FDA-approved JAK1/2 inhibitor, known as ruxolitinib, and the data are out there to support its utilization in this patient population.  

Transcript edited for clarity.

August 2014

  • A 67-year-old female is diagnosed PV after complaining of fatigue
  • Physical Exam was unremarkable
  • CBC:
    • HCT, 48%
    • WBC, 12,100/μL
    • Platelets, 603,000/μL
  • Mutation testing: JAK2 V617F-positive
  • The patient was started on treatment with low-dose aspirin and hydroxyurea 500 mg/day
  • Her symptoms resolved within 3 months

February 2016

  • She now complains of left upper quadrant pain
  • For 1.5 years, the patient was maintained on treatment; however, for the past 9 months her hematocrit has risen to 48% and she has required 4 phlebotomies in last 6 months
  • Hydroxyurea was increased from 500 mg to 1,000 mg daily
  • Physical Exam: remarkable for splenomegaly

August 2016

  • Physical Exam: still remarkable for splenomegaly, slightly smaller
  • HCT 47.5%
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