Risk Stratification in Polycythemia Vera

Jamile M. Shammo, MD:Once a diagnosis is made, then I think physicians need to think about risk stratification for those patients, because this is how the therapeutic guidelines were formatted, if you will, depending on risk of thrombosis for this patient population. And traditionally speaking, patients are assessed depending on their age and prior thrombotic events. Clearly, if you had someone who had a prior thrombotic event, they’re at a higher risk of thrombosis to begin with based on the fact that they had already had one. And, of course, with age, there’s an increase in the rate of thromboses, which was also demonstrated in the ECLAP study. The data have already been published and people are well aware of what it had shown, which is the reason why age and thrombosis history represent the traditional risk stratification for those patients. So, if I have a high-risk patient, based on either one of the two factors I mentioned, then I think cytoreduction needs to be considered.

Low-risk patients will benefit from phlebotomy to maintain their hematocrit below 45%. There are data supporting why hematocrit below 45% should be pursued. And everybody should get an aspirin. Again, the platelet count needs to be monitored in this fashion, because you want to prevent bleeding events in someone who may have an excessively high platelet count because they have acquired von Willebrand refractory disease. That’s something that clinicians also must pay attention to.

There are additional cardiovascular risk factors that have not been included in the traditional risk stratification. But I think, in general, physicians realize that someone who has high blood pressure, someone who has diabetes, someone who has hypercholesterolemia, those patients have a higher risk of cardiovascular events to begin with. So, when I’m evaluating a patient relative to their risk, I do take these into consideration. I suppose it may play into someone who may be younger, for example, like less than 60 or 65 years of age, and may not have had a thrombotic event. But if they have all of those factors, then I think they have to be taken into consideration and figured into how you would approach this patient. I think perhaps PV patients have to be evaluated on a patient-by-patient basis relative to their risk.

So, to follow up on the cardiovascular risk factors, I think every time I meet with a patient who has PV, we talk about smoking and we talk about controlling many of those risk factors that we have discussed—controlling their cholesterol level, perhaps taking care of the blood pressure issue, and making sure that it’s optimized, living a healthy life, perhaps exercising. Reducing their chances of having complications related to cardiovascular thrombotic events is very important.

The way I think about goals of therapy in people who have PV, it’s a 2-pronged approach. One is optimization of blood count, and we can talk about how extremely important it is to actually have a hematological response when you initiate therapy. So, that would be one aspect of it. And the other one, obviously, is controlling symptoms. We are physicians and the goal of taking care of patients is to improve their symptomatology without adding further toxicity from whatever agent you plan to utilize. So, that would also be something that figures into my choice of therapy.

Why is optimizing hematological parameters important? Well, it has been shown that a hematocrit below 45% reduces the risk of major cardiovascular events and major thrombosis of about four-fold, and this was shown in a randomized perspective session in the CYTO-PV study. So, I tend to be extremely diligent about keeping hematocrit below 45%. Why? Because this is one area where I can control this. Although I have to say that even in those prospective trials, a group of patients, for whatever reason, had a higher hematocrit greater than 45% despite all intensive efforts to keep it below 45%. It’s very important for us as treating physicians to identify this patient population, figure out exactly how you can optimize their hemoglobin a little bit better. And in my opinion, I think we need to look at their iron status, probably we have to talk to them about compliance, perhaps, and maybe assess the dose of the medicine that they are taking.

And then, the second area is their symptom control, and that figures into their quality of life. They’re going to be living with disease for many years to come and you want them to be able to have reasonable control of symptoms, that they can go on with a reasonable preservation of their quality of life.

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%