Individualizing Treatment Approaches in MPN - Episode 3
Key opinion leaders discuss treatment goals, considerations, and guideline recommendations for patients with low- or high-risk polycythemia vera.
Ruben A. Mesa, MD: When we begin with the concept of disease burden for a patient with P [polycythemia] vera, 1 has a discussion. I had that discussion with a patient today. Our goals with P vera are to keep the disease as invisible in the life of the afflicted patient as possible. That begins with trying to diminish the risk of thrombosis or bleeding. We know that key factors are control of the hematocrit—typically in low-risk patients with phlebotomy, to keep a strict hematocrit of under 45%. Recent trials show that keeping individuals under 45% is beneficial and has a differential effect in decreasing the risk of thrombosis or bleeding. There are individuals that sometimes need a more targeted approach based on their symptoms or other disease-related features, but 45% should be the ceiling.
Additionally, we use low-dose aspirin assuming there is not an aspirin allergy or other contraindication. This can help with symptoms but also help decrease that risk.
Another goal with low-risk PV is making sure that the therapies we’re using are adequately addressing the difficulties a patient has. There are low-risk patients who are symptomatic or don’t tolerate phlebotomy to the degree that we wish they could. In those circumstances, that might be an indication to consider a change in therapy or the addition of cytoreductive therapy. Indeed, our group presented an analysis at ASH [American Society of Hematology Annual Meeting] looking at low-risk patients and showed that there are many individuals, perhaps up to half, who have had cytoreductive therapy at some point during the course of their disease for some of these gaps that can exist with management, using solely phlebotomy and aspirin.
Srdan Verstovsek, MD, PhD: NCCN [National Comprehensive Cancer Network] Guidelines utilize a simple way of dividing patients into low risk for thrombosis and high risk for thrombosis when we talk about PV [polycythemia vera]. High risk is defined by age over 60 or a history of blood clotting. Roughly, two-thirds of the patients are such.
What do we do about this? We start the phlebotomy, like in other patients. That would decrease the hematocrit, and the goal is below 45%. We give patients baby aspirin. That’s to decrease the stickiness between the cells. In high-risk patients, we also start hydroxyurea or the guidelines would say pegylated interferon. These are 2 alternatives as a cytoreductive therapy. We want to decrease the numbers. We want to maintain constantly hematocrit below 45%, normalize the white blood cells and platelets if we can, and control the quality of life. The symptoms and the symptomatic splenomegaly should be controlled if possible.
The hydroxyurea is a pill. You take it daily, and it works in many patients. But it may not work optimally, meaning controlling these factors in everybody. Retrospective chart reviews identified that about 40% of the patients are managed, 40% suboptimally, and 20% not optimally at all. They are resistant, refractory, or intolerant. That comes from retrospective chart reviews, because there was never a formal study of hydroxyurea to assess the benefits through these parameters. It’s just that historically we have been using it for 50 years.
Occasionally there are adverse effects, ulcers or skin sores down on the legs, low-grade fevers, loss of hair, indigestion. Maybe 10% of the patients may have them. We monitor for myelosuppression as well, not just for these nonhematologic parameters. We want to make sure it’s not suppressing the counts too much. Of course, we then want to optimize the therapy. We want to make sure it’s controlling the blood cell count symptoms in the spleen. If it does not, you still need phlebotomies. White blood cell counts and platelets are still high, the spleen is symptomatic, patients have a lot of systemic systems—any of these would identify patients that are not optimally managed. Maybe they’re even resistant or refractory. In that case, you would perhaps choose something else, like a second-line therapy.
Every patient with high-risk disease should be given cytoreduction. But if the patient is younger, let’s say a 25-year-old has PV and blood clot, we would not give hydroxyurea to that patient. Pegylated interferon is the norm, because that’s a biological agent. It’s given as an injection under the skin once a week at the beginning, perhaps less often later. Particularly in younger people, because of the durability or a need for durable cytoreduction control, we stay away from chemotherapy. Hydroxyurea is a chemotherapy. We use interferon, pegylated interferons, that are long lasting or long acting can be given to older folks as well. They’re much safer. NCCN Guidelines would identify hydrea or interferon—hydrea in most patients, but interferon has a role and maybe even more than we would like to accept, much more in the older patients as well, particularly because it’s a biological agent and can potentially change the bone marrow environment, affect the malignant clone. These are potentials of this therapy that are to be explored.
Transcript Edited for Clarity