Optimizing Treatment in Myeloproliferative Neoplasms - Episode 14
Transcript:Daniel J. DeAngelo, MD, PhD: When I see a patient with polycythemia vera for the first time, I assess their risk score based on age, white blood cell count, history of thrombosis, and cardiovascular or cerebrovascular disease. I try to control what I can control. For patients who can tolerate aspirin therapy, I initiate an aspirin, and then I try to have strict control of the hematocrit to try and bring the hematocrit to less than 45%. And a lot of that will depend upon how the patient presents. If a patient presents with an extremely high hematocrit, then I’m going to be more aggressive in trying to reduce that right away with phlebotomy weekly, maybe twice weekly for severe cases. For other patients, I may initiate a phlebotomy strategy of every-other-week to get the patient under control. But, I’ll routinely measure a patient once I can get the hematocrit less than 45% on an every-2-week or every month basis until I’m comfortable that the patient’s hematocrit is well controlled to less than 45%. And then, in those patients, I’ll start extending out the monitoring to every 2 months or every 3 months. But, initially, when you first see a patient, it’s important to bring the hematocrit down relatively rapidly, and then to follow the patient carefully—again dependent upon the initial presentation—over a first period of time to assure that the patient is having adequate control and maintaining a hematocrit of less than 45%.
Srdan Verstovsek, MD, PhD: The goal of therapy for polycythemia vera, first of all, is to control hematocrit. A 45% or lower hematocrit has been, for many years, the main goal of therapy, which can be achieved by phlebotomy and, in those that need cytoreductive therapy, with additional medications. Until 2013, the question was whether this is really a valid target because it was based on animal studies. Now, Dr. Marchioli and his colleagues published a major paper in The New England Journal of Medicine, in January 2013, that clarified and determined that this actually is correct. What they did was they randomized patients between controlling the hematocrit below 45% strictly or not, having hematocrit below 50%—so between 45% and 50%. In that setting, the patients that had a strict control of hematocrit below 45% had the better outcome, less cardiovascular events, less thrombotic events, and less mortality, meaning fewer patients were dying from the complications. I think that’s clear evidence that we have been right to suggest that the strict control of hematocrit below 45% must be implemented for overall best outcome of the patient with PV.
Daniel J. DeAngelo, MD, PhD: There are few randomized studies in polycythemia vera. There’s the ECLAP study, which randomized patients to low-dose aspirin versus no aspirin, showing a benefit for aspirin. Then, there’s the CYTO-PV study, done by our Italian colleagues, looking at controlling hematocrit of under 45% versus greater than 45%. There are just simply no data suggesting that an intermediate value is of the same quality in terms of reducing cardiovascular mortality. As I always say, the data are the data, and if you want to maintain a patient free of cardiovascular disease, which is the goal of therapy for patients with polycythemia vera, you need to follow the data. And the data suggest that patients have a better outcome, improved survival with respect to cardiovascular mortality, if their hematocrit is maintained less than 45%. So, that’s the approach that I take.
Kim-Hien T. Dao, DO, PhD: The way that I determine uncontrolled PV is I look at their hematocrit control with the treatment that has been outlined. So, for example, a patient who’s on phlebotomy only, I check to see what the hematocrit is between the phlebotomy procedures. If every time I check, their hemoglobin or hematocrit is elevated above the goal, I know that probably in between the blood checks they are uncontrolled, and that places them at high risk for thrombotic events. And so, if I’m finding that every time I check, they’re needing a phlebotomy, it means that I’m not checking enough and that probably the phlebotomy is not frequent enough to control their hematocrit.
In terms of what is an okay frequency of phlebotomy, this is individualized based on the patient. Some patients find phlebotomy to be a cumbersome process. They don’t like it or they have symptoms like dizziness associated with phlebotomy. So, for some of them, it’s more significant than others. Others prefer phlebotomy over getting treatment with hydroxyurea or ruxolitinib. In those situations, I think we can tailor our treatment plan according to the patient. But, I think this is variable between patients because some see phlebotomy as very well tolerated and not an issue, and others feel like it’s a quality of life-limiting issue or impacting their quality of life enough that they would consider a drug therapy.
Transcript Edited for Clarity