Expert Discusses Recent Developments in Polycythemia Vera

Srdan Verstovsek, MD, PhD

Ruxolitinib (Jakafi) and hydroxyurea have opened the doors to further potential treatments for patients with polycythemia vera (PV).

In an interview withTargeted Oncology, Srdan Verstovsek, MD, PhD, of the University of Texas MD Anderson Cancer Center, discusses the challenges of PV, the impact of the approval of ruxolitinib, and ongoing trials that could further impact the disease type.

TARGETED ONCOLOGY:What are the biggest recent developments in PV?

Verstovsek:

In polycythemia vera, we have had significant development in the last couple of years. This is a relatively short time for this disease to have such novelties because since 65 years ago, when we identified this disease, not much has happened.

Now we have several developments. One that we have that's more recent is a new modified way of diagnosing polycythemia vera. The thresholds for diagnosing PV based off of high red blood cell count has been lowered. The threshold has been lowered to account for our ability to identify patients with so called “masked PV.” These are patients with the iron deficiency that is usually present in polycythemia vera, patients with low blood cell count, and sometimes patients that have both lower counts and have an iron deficiency.

The second most important part of a modified diagnostic criteria is a need for a bone marrow biopsy. This is usually accompanied by testing forJAK2mutations, and we have 2 mutations to talk about;JAK2V617F, orJAK2exon 12. A combination of these factors leads to a determination of the proper diagnosis of PV. It's very important to understand that lowering the threshold of the red blood cell count can lead to such identification of patients.

TARGETED ONCOLOGY:What is the current role of hydroxyurea in PV?

Verstovsek:

It is important that we recognize, or understand better, the benefit of frontline therapy with hydroxyurea. This is done for patients with a high risk of thrombosis; these are patients that are usually over 60 or have a history of thrombosis. This is the definition of a high-risk patient for thrombosis. These patients require cytoreductive therapy to lower the blood cell count.

We can look at the benefit of any therapy in 5 different ways. It used to be that we would look at red blood cell count control only, however, now we also look at the control of white cells—they're elevated in many patients—and also the control of platelets that may be high, and their symptoms. So we have 5 things to look at, and looking at these 5 factors we now know that hydroxyurea in fact does not work very well in about a quarter of the patients. It does work very well in a quarter of the patients, but in others it's kind of a mixed bag. These patients may in fact require a different therapy.

Here's where the real novelty of this exercise is, not only to understand the full benefit of hydroxyurea and identify the patients that don't have a benefit, but this led to a new approval of a new medication called ruxolitinib that we now have at our disposal to treat patients who are intolerant of or resistant to hydroxyurea. It was approved about a year ago as a second-line therapy for PV patients.

TARGETED ONCOLOGY:What impact has ruxolitinib had in the field of PV?

Verstovsek:

Further analysis of the patients on hydroxyurea identified factors that led us to conclude that the patient was not deriving a good benefit or had developed a resistance to hydroxyurea. Patients who are resistant to hydroxyurea have a shorter life expectancy, more aggressive disease, they contract myelofibrosis much more often, and faster. The biology here is that these patients are at an increased risk. The benefit of a new therapy, like a JAK inhibitor like ruxolitinib, is that we can manage these patients not only for risk of thrombosis, but also possibly decrease the progression of the disease, or complications that come with the disease. The main reason for death in these patients is thrombotic events from uncontrolled events.

TARGETED ONCOLOGY:What's on the horizon for PV?

Verstovsek:

The new way of looking at therapeutic potential in polycythemia vera includes refinement of the understanding of the complete benefit of hydroxyurea, which is our first agent, or ruxolitinib for the second-line. There is much more to be done. It is fine where we are right now with all of these developments of the last several years, but we know very well that there are other agents active in the space of PV, in particular interferons. These are biological agents that are given to patients as injections, and they have been active in this area and are marred by increased toxicity. A third of the patients usually stop therapy with interferon, the classic interferon that is given under the skin 3 to 5 times per week, and that is not usually acceptable for long-term use.