Updates in Polycythemia Vera Treatment and Management
Gabriela Hobbs, MD, Massachusetts General Hospital, Boston, Massachusetts, providesan overview of the latest strategies and updates regarding the management and treatment of patients with polycythemia vera (PV), including reviewing the National Comprehensive Cancer Network (NCCN) guidelines on utilizing ropeginterferon alfa-2b as a first-line agent for the treatment of patients with both low-risk and high-risk disease.
Transcript:
Hello, my name is Gaby Hobbs and I'm the clinical director of the leukemia service at the Mass General Hospital in Boston, Massachusetts. Today I'm going to talk about updates in the management of polycythemia vera.
First, I'll start with an overview and the primary clinical goals of treating patients with polycythemia vera. PV is one of the myeloproliferative neoplasms, and although it's most generally characterized by erythrocytosis, patients can present with panmyelosis with high white counts and high platelets as well.
The primary goal of managing patients with PV, up until this point, has been to prevent thrombotic complications, which is the most common complication faced by patients living with PV. However, managing the symptoms that may be associated with PV is also an important goal. And something that we have all been very interested in working on is to prevent disease progression and modify the underlying disease biology.
Some of the challenges in managing patients with PV is that this is a chronic myeloproliferative neoplasm, and patients may live with anxiety knowing that this disease is going to progress, or can have the potential for progressing. Although, as I mentioned before, one of the most common complications of this disease is related to thrombotic complications. Managing these patients requires being very diligent in blood count control in order to prevent thrombotic complications. Most patients with PV will be treated with an aspirin for thrombotic prevention. I think that along with that, lifestyle modification and modifying cardiovascular risk factors is also very important. This can really help empower patients, as they are partners in managing their care.
Some of the challenges of treating patients with PV also include that phlebotomy is currently still a standard in helping patients, especially those with low-risk PV, to have adequate phlebotomy control, with the goal of reaching a hematocrit of less than 45. Although many patients tolerate phlebotomy fine, for some patients it may be difficult. For some it may be associated with the development of fatigue from iron deficiency, and from some it may just be difficult in that they may still require several phlebotomies per month in order to maintain that hematocrit at that level of less than 45. That has challenges as patients may develop reactive thrombocytosis from iron deficiency.
The therapies that we have available are generally well-tolerated, but certainly there's some patients that still can't tolerate those treatments well for a variety of reasons—either because they don't control their blood counts adequately, or they lead to other side effects. The most common medications that are utilized to treat patients with PV are hydroxyurea, and then interferons and ruxolitinib (Jakafi).
Today I'm going to focus a little bit on interferons. First I'm going to talk about the PEGINVERA study that led to the FDA approval of ropeginterferon alfa-2b for the management of both low-risk and high-risk PV. Interferons have been utilized for the management of PV patients for many decades. First we had [non-]pegylated interferons that were associated with a lot of side effects, that needed to be administered multiple times a week. After that came the pegylated interferons, of which Pegysus is commonly used in the United States. That's administered once a week and is definitely more well-tolerated.
More recently we've had the approval of ropeginterferon. Ropeginterferon was approved based on the PEGINVERA study, which was a phase 1/2 prospective, open-label ,multicenter study that investigated the efficacy and safety of ropeginterferon for patients with a confirmed diagnosis of polycythemia vera. Regardless of whether or not they had been on prior cytoreduction. After 1 year of treatment, patients could switch from the treatment every 2 weeks, to a 4-week dosing regimen. And what they found in this study was that a significant percentage of patients had a complete hematologic response, 64% of patients, and 33% of patients had a partial response. In addition to the complete hematologic response, they found that switching from a 2-week dosing regimen to a 4-week dosing regimen didn't have an impact on response, but certainly it's much easier for patients, who only need to do a subcutaneous injection once a month.
An area of interest is that the JAK2 allele burden went down in a significant percentage of patients. So 12 of the 42 patients had a complete response in their JAK2 allele burden, and then 45%, or 19 out of 42 patients, had a partial response. That's something that we all are following closely and are very interested in understanding whether or not that has the potential for modifying the disease biology of PV, and if it can prevent progression to myelofibrosis and to acute [myeloid] leukemia.
Based on the PEGINVERA study as well as the CONTINUATION-PV and PROUD-PV studies, the NCCN guidelines now recommend ropeginterferon alfa as a preferred first-line agent for both low-risk patients and high-risk patients. The low-risk part is almost more significant than the high-risk inclusion. For patients that have high-risk polycythemia vera, we have always recommended cytoreduction, and cytoreduction has included the option of pegylated interferon, or interferon in general, as well as hydroxyurea in the first-line and ruxolitinib in the second-line.
However, for first-line for low-risk patients, cytoreduction had generally not been included as a recommendation. The upfront treatment of low-risk patients, those that are younger than 60 and have not had a thrombotic event, usually were managed with aspirin and phlebotomy alone. Cytoreduction for that group of patients was recommended based on whether or not they had symptoms that were not adequately controlled with phlebotomy, or blood counts that were not adequately controlled with phlebotomy. However, the NCCN states that ropeginterferon can be utilized just for blood count control in that group of patients, irrespective of whether or not they're doing well with phlebotomy, or their symptoms are not well-controlled. That recommendation was based on the LOW-PV study that studied low-dose ropeginterferon for these low-risk patients, and found, not surprisingly, that utilizing low-dose ropeginterferon was better at controlling blood counts than phlebotomy.
This gives an option for younger patients to be treated with cytoreduction. I think the excitement that's come with that recommendation is not just that we can utilize something that seems a bit more modern than phlebotomy alone, but also that we know from several studies with long-term follow-up, that the JAK2 allele burden does go down consistently, and in some cases very significantly, with the use of ropeginterferon, and interferon in general, in these patients. I look forward to having longer-term follow-up to see if some of these low-risk patients end up having less chances of progressing to myelofibrosis and acute leukemia.
When thinking of managing polycythemia vera, I would say that 1 thing that's important to keep in mind is that we do have more treatment options for our patients with PV. Now we understand the disease better. When adopting a new treatment such as ropeginterferon, the advice that I would give to clinicians that treat patients with PV is that ropeginterferon is really a new generation of interferons. It’s associated with fairly manageable and mild side effects, and if we compare this interferon to the initial interferons, it's like dealing with very different medications.
Ropeginterferon comes in a pre-filled syringe, making it very easy for patients to administer that at home. The once every 2 week dosing initially is also fairly easy, and then patients can be transitioned to once a month dosing. So really the burden for the patients is just not that significant. I would recommend patients to utilize this medication if they're good candidates for that, and for clinicians to think about ropeginterferon as almost a different medication, and not compared to the older interferons where there were a lot of side effects.
That being said, it is still important to be aware that is still a medication that can be associated with side effects. Some of the common side effects that we are used to thinking about with interferon include transaminitis, autoimmune issues with thyroid dysfunction being the most common; depression can occur, although it's infrequent. In addition to that, some patients can develop significant itching from ropeginterferon. So being aware that that could be a complication of this treatment is important, as patients with PV may suffer from itching from their disease as well, and sometimes it's difficult to know which of the 2 it is. I hope you have found this section useful, and thank you so much for your attention.
