Expert Highlights Ongoing Research in MPNs

Srdan Verstovsek, MD, PhD

Srdan Verstovsek, MD, PhD

Although myeloproliferative neoplasms (MPNs) such as essential thrombocytopenia (ET) and polycythemia vera (PV) are more easily controlled than myelofibrosis, another MPN, these conditions still have limited treatment options approved by the FDA, according to Srdan Verstovsek, MD, PhD.

“We are making progress in developing medications for patients with MPNs, but we are in need of a team effort to achieve this goal,” said Verstovsek, director of the Hanns A. Pielenz Clinical Research Center for MPNs at The University of Texas MD Anderson Cancer Center.

Clinical trials are necessary in improving the treatment landscape for patients with ET and PV. Verstovsek encouraged community oncologists to seek out clinical trials at larger centers such as his and participate when possible.

“In many cases, we know that these clinical trials can be more effective than the best available therapy,” said Verstovsek. “I encourage them to participate in them if they are not already participating.”

In an interview withTargeted Oncology, Verstovsek discussed the current treatment landscape for patients with ET or PV and shared details of ongoing clinical trials in the field.

TARGETED ONCOLOGY:Can you start by discussing the current treatment landscape for MPNs?

Verstovsek: There are several types of MPNs, quite a few actually. When we talk about classic ones, people usually talk about ET, PV, and myelofibrosis. ET and PV are considered rather benign because in most of the patients, these conditions can be controlled well in terms of the thrombotic risk that they carry by controlling their blood cell count and providing medications necessary to control those numbers and controlling the symptoms.

Standard therapy in ET, when it’s needed, is hydroxyurea. This is a chemotherapy that is taken by mouth, usually indicated for people older than 60 or who have a history of blood clotting. Otherwise, everybody is subject to a baby aspirin too if there are no contraindications. In some patients, we do prescribe interferon, particularly long-acting interferon, which is a biological agent that is given as injection once a week. It’s usually given in people who are younger, so we don’t expose them to a long-term chemotherapy like hydroxyurea which would be taken for decades, or in the young females that want to be pregnant and need something to control blood cell count.

In this setting, after hydroxyurea, or occasionally after interferon if that’s the choice, anagrelide (Agrylin) has been approved and is used as a second-line therapy in most of the patients, another pill to control the platelet numbers. This is the standard of care, hydroxyurea followed by anagrelide, and in some patients, interferon.

In PV, not only are platelets high but also red blood cell count is high in everybody. About 60% of patients will have high platelets and about the same number of patients will have high white cells. In PV, everything grows. The priority is to control the red blood cell count, which is usually achieved with a phlebotomy.In some patients, being those that are older than 60 or have a history of blood clotting, similar to what I was saying about ET, these are some of the factors that would lead us to utilize medications early to normalize the blood cell count with cytoreductive therapy.

Usually, the first choice is hydroxyurea, the same medication as in ET, [it’s a] chemotherapy that is taken by mouth every day as a pill. Second-line, it’s not anagrelide anymore because anagrelide is only for platelets. It’s actually ruxolitinib (Jakafi), a JAK inhibitor. As with ET, in some patients we use interferon. Standard practice is usually again in younger patients who need cytoreductive therapy, which is not common but is possible, or in females who do want to become pregnant, so the interferon biological agent is preferred.

TARGETED ONCOLOGY:What clinical trials are you involved in for ET?

Verstovsek:Again, [there is] normal life expectancy, [but] the problem is thrombosis, control of the blood cell count. People that need to have it controlled is first achieved by hydroxyurea. Second-line is anagrelide. The studies in ET are not very common, but there is 1 worth mentioning. In a blinded way, ruxolitinib is being compared to anagrelide in people with ET who were on hydroxyurea, but the hydroxyurea did not work and caused toxicities.

Hematocrit control of the disease, you can say in those who are resistant or refractory or intolerant to hydroxyurea, these people are subject to a clinical study where in a blinded way over 1 year, people are treated either with ruxolitinib or anagrelide in order to control the platelet, white blood cells, and the symptoms. White cell count can sometimes be increased in ET, not too often, in 10% of the patients. That study is underway which may lead to the approval of ruxolitinib as a second-line agent if found superior to anagrelide.

TARGETED ONCOLOGY:What clinical trials are you involved in for PV?

Verstovsek:As I explained, the standard practice is hydroxyurea followed by ruxolitinib, but there are attempts to compare in the frontline setting hydroxyurea to long-acting interferon. The standard guidelines for therapy for PV say that people who do need cytoreductive therapy, people older than 60 or have a history of thrombosis, would have hydroxyurea or interferon. This is interesting, because interferon has been used in PV quite often in the past, but it has many side effects.

The long-acting interferon given weekly or every other week are being tested now in comparison to hydroxyurea, and there were several studies presented last month at the ASH Annual Meeting that suggested there is no real benefit of interferon over hydroxyurea in terms of controlling the blood cell count or symptoms, so equal activity, which is good. There was 1 study from Europe that suggested that 1 of those new long-acting interferons, called ropeginterferon alfa-2b, may actually be superior to hydroxyurea in the frontline setting in PV patients. Recently, we learned that this agent is going to be approved in Europe by the European Medical Association. It’s a standard therapy for PV along with hydroxyurea. Hopefully, these studies will be done here with the same medication in the United States, so our patients can benefit from it in the future.

TARGETED ONCOLOGY:What do you hope will come out of this research?

Verstovsek:If ruxolitinib is found superior to anagrelide in the second-line setting, then we will have another medication that will hopefully help patients with ET, particularly those who do not do well symptom-wise. Ruxolitinib is good for controlling symptoms in addition to controlling the blood cell count.