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Expert Highlights Advances in Myeloproliferative Neoplasms

Gina Columbus @ginacolumbusonc
Published: Tuesday, Nov 01, 2016

Srdan Verstovsek, MD, PhD

Srdan Verstovsek, MD, PhD

Both myelofibrosis and polycythemia vera (PV), are myeloproliferative neoplasms with very specific characteristics and treatment strategies, explains Srdan Verstovsek, MD, PhD.

One of those strategies was confirmed in June 2016, with the final 5-year efficacy and safety results of the phase III COMFORT-I study. The trial confirmed earlier findings of a significant benefit in intermediate-2 and high-risk patients with myelofibrosis who were treated with the JAK-2 inhibitor ruxolitinib (Jakafi).

In the patients randomized to ruxolitinib, 59% had a ≥35% reduction in spleen volume at any point on study. The median duration of response was 168.3 weeks (95% CI, 107.7-NE). At a median follow-up of 268.4 weeks, the overall survival was not reached in the ruxolitinib arm and 200 weeks in the placebo arm (HR, 0.69; 95%, CI, 0.50-0.96; P = .025).

Verstovsek discussed treatment strategies for myeloproliferative neoplasms during the 2016 OncLive State of the Science Summit on Treatment of Hematologic Malignancies.

In an interview with OncLive, Verstovsek, a professor in the Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer, discussed the diagnosis and treatment options for PV and myelofibrosis.

OncLive: Let’s first discuss myelofibrosis. How would you characterize this disease?

Verstovsek: Myelofibrosis is 1 of the myeloproliferative neoplasms—a chronic disease of the bone marrow. It is, unfortunately the aggressive type. It does affect the life expectancy of the patients. The average survival is about 5 to 7 years. Unlike other myeloproliferative neoplasms—and the name implies that these myeloid cells, they’re the bone marrow cells—grow without control and overwhelm the bone marrow and blood.

It is a disease that we would perhaps even call chronic leukemia. Many patients come and ask, “Is it cancer?” Yes, it is a cancer. It does kill people. The underlying biological problem is hyperactivity of the JAK/STAT pathway as is in other myeloproliferative neoplasms, essential thrombocythemia and polycythemia vera. There are reasons for this intracellular signaling pathway to be active and leads to a disease that is mutation driven.

The 3 mutations are JAK2 V617F, calreticulin, and MPL. These 3 mutations lead to hyperactivity of JAK/STAT pathway as uniform biological abnormality in every patient. Even if you don’t test patients for any of these driver mutations, which is advisable as part of the diagnostic process, know that there is a hyperactivity of JAK/STAT pathway in that patient.

How are patients typically diagnosed?

Myelofibrosis is a disease of the bone marrow where there is a reaction to the presence of malignant cells by developing fibers. Therefore, the bone marrow biopsy is a cornerstone of the diagnostic process for myelofibrosis. However, you cannot really diagnose myelofibrosis only based on a bone marrow biopsy. In fact, there is no 1 test that will diagnose myelofibrosis.

There are criteria that need to be fulfilled and this includes looking at the blood cell count, presence of anemia, leukoerythroblastic reaction, bone marrow cells in blood, systemic symptoms, and an increase in lactate dehydrogenase. This is a task that clinicians need to undertake, putting things together and having a final diagnosis of myelofibrosis.

What are the goals of therapy in intermediate-risk patients and what is the standard of care for them?

Within myelofibrosis, we have usually 4 types of patients based on the prognostications of their longevity. The low-risk patients have an average survival of 11 years, intermediate-risk patients 4 or 8 years, and then high-risk patients 2 years. Ruxolitinib is indicated in the United States for patients with intermediate- or high-risk of dying. Ruxolitinib is certainly a very good choice and it will, in a great majority of the patients, control the signs and symptoms, and eventually make people live longer.

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