Ruben A. Mesa, MD, FACP:When planning my treatment options for patients with polycythemia vera [PV], I first consider their risk and their disease burden. How likely are they to have blood clots or bleeding? And then, what is their burden as it relates to that risk as well as symptoms and splenomegaly?
First, I view that all patients benefit from control of the hematocrit. I think that part is very clearwith a hematocrit that is clearly under 45% pretty much at all times for all patients with polycythemia vera.
There are individual patients who may benefit from that being a little lowerperhaps in women, perhaps in people in which that’s inadequate for their symptoms. The limitations of phlebotomy are it can be hard on the veins, it can lead to iron deficiency, it might exacerbate some of the disease-associated symptoms. Sometimes that’s where medical therapy, in that control, comes into play. But we need to maintain a hematocrit under 45% at all times for all PV patients after diagnosis.
Second, aspirin. There have been randomized studies [that] clearly show that a low-dose baby aspirin is helpful in patients with PV, particularly high-risk PV. Given that aspirin is a fairly benign therapy, we largely recommend low-dose aspirin81 mg, or 100 mg in Europe—for all patients with PV. Limitations just being if you’re aspirin allergic or are already on warfarin or other blood thinners. Then it may exacerbate the risk of bleeding. If somebody is already on other antiplatelet therapy, we may be able to just leave them on clopidogrel or what other therapy they were on.
In many individuals, the limitation of both of these therapiesphlebotomy and aspirin—is that they don’t fully control all those aspects of the burden of the disease. Our current guidelines for a response in PV includes a control of symptoms, control of splenomegaly, and having blood counts adequately controlled—the white cells, the platelets, and the red cells.
If a patient is on phlebotomy and aspirin, it may help the symptoms some. It may help the red cells, but it’s not going to do anything for the white cells, the platelets, the spleen, and sometimes multiple other symptoms.
I believe that the majority of patients with PV benefit from cytoreductive therapy. Our current frontline cytoreductive therapy is either hydroxyurea or interferon, according to our current NCCN [National Comprehensive Cancer Network] Guidelines. Hydroxyurea is a pill. It is simple to take for most. Its downside is that it’s a nonspecific therapy, and it can lead to neutropenia or thrombocytopenia. It frequently is just not active enough against symptoms, splenomegaly, or other difficulties that people may have. It can increase the risk of cutaneous malignancies. Controversially, it may have a slight impact in increasing the long-term risk of acute leukemia. That’s difficult to prove, but it’s also very difficult to disprove. I find that hydroxyurea, where it lets us down, is really in the limitation of its activity. It’s a very nonspecific therapy, best used for controlling the counts, but it frequently leaves us disappointed with other potential goals.
Interferons, or the long-acting interferons, and now the pegylated interferon alfa-2b in Europe, is an additional frontline therapy. It is an injectable agent. It’s a biologic agent administered once to twice a week. It can help to lower the counts. It may help to improve symptoms, particularly if they’re related to the counts. Its impact on splenomegaly is probably less. Indeed, the European indication is for PV patients who don’t have splenomegaly. Its impact on significant symptoms is probably more modest. Between hydroxyurea and interferon there is a hope, a hope more than being truly proven beyond a shadow of a doubt at this moment, that it may have a greater impact on delaying disease progression.
Now, in many individuals, this frontline therapy will be inadequate. For those who fail hydroxyurea, in particular, we have ruxolitinib approved as a therapy. This is a JAK1 and JAK2 inhibitor that is particularly helpful in controlling the hematocrit for individuals who are continuing to have difficulty but have a need for phlebotomies, have become intolerant for phlebotomy, have progressive splenomegaly, have difficult symptoms, or have been resistant or intolerant to hydroxyurea. That medication, as well, is an oral medication. It’s a pill. Its limitations are not many. It perhaps has the greatest activity against splenomegaly and symptoms of any of the PV medications. Its toxicities that we monitor for are an increased risk of herpes, or shingles, and the potential of lowering blood counts. There is also a slightly higher risk for nonmelanoma skin cancers.
Transcript edited for clarity.
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