Srdan Verstovsek, MD PhD; and Jamile M. Shammo, MD
Srdan Verstovsek, MD, PhD, and Jamile M. Shammo, MD, discuss the heterogeneity of clinical presentation and underlying biology of polycythemia vera, as well as the development of new guidelines for myeloproliferative neoplasms.
Srdan Verstovsek, MD, PhD: It really depends from 1 center to another center on experience in seeing myeloproliferative neoplasm patients. And I will tell you that my experience is seeing about 200 patients a year. Most of the patients, about 60%, will be patients with myelofibrosis, which makes sense because these are patients with more aggressive condition. They have a shorter life expectancy, but we also see patients with ET, essential thrombocythemia, or PV, polycythemia vera, particularly those that do not do well with standard therapies.
Jamile M. Shammo, MD: Patients have heterogeneous presentation and symptomatology. Some patients I have had the diagnosis made by chance. Someone did a CBC and their hematocrit was 52 or something, and then the workup shows PV and they really have no symptoms. But then, I always wonder, how much time have we spent digging out how many symptoms do they have? But truly there is a subset of patients, albeit it small, who basically have no symptoms.
Other patients may come in with an enlarged spleen, night sweats, and fever. And then, I guess the other thing is that, how often do we actually do bone marrow biopsies on those patients? Perhaps it may have to do with the chronicity of the disease, how long they’ve been living with it, and what is there; the fibrosis in the bone marrow? And, again, those questions and concerns all figure into the clinical presentation. So, yes, I would say it probably has to do something with how long they’ve been living with it and some other factors, too, that deal with their underlying comorbidities that might influence how they present.
Srdan Verstovsek, MD, PhD: When the JAK2 V617F mutation was identified in 2005, there was the expectation that this might have been a driver mutation that actually leads to the disease existence and progression, but that’s not the case. It’s not quite the case because there are other mutations that do the same job as the JAK2 mutation. These are MPL, or mipple, mutations in the receptor for thrombopoietin, a growth factor for platelets, and mutations in calreticulin. So, calreticulin, MPL, and JAK2 mutations do the same job. They activate the JAK/STAT pathway. This is a hyperactive intracellularly pathway in the cells in the bone marrow that makes cells to grow and it causes some inflammation among the other ones. So, we have hyperproliferation and inflammation as 2 major problems in myelofibrosis in particular.
Since the discovery of the JAK2 mutations some 10 years ago, we have accumulated a lot of knowledge about the biology of MPNs and myelofibrosis in particular. The field is evolving. We are learning more, not just about biology but about therapy as well. The discovery of the JAK2 mutation led eventually to approval of a first medication for myelofibrosis. Patients with intermediate- or high-risk disease can be treated now with ruxolitinib, a JAK inhibitor that inhibits the JAK/STAT pathway.
It’s the same for second-line therapy in PV. So, there was a need in the United States for development of specific guidelines—how to manage patients with MPNs in everyday practice. And myelofibrosis, being the most aggressive, was the first one for which we developed the guidelines. The NCCN guidelines are now available in print and online. They tell you that first you assess the risk of dying in patients with MPN, in myelofibrosis in particular, you refer them to transplant, but then treat them for clinically relevant problems, including for anemia with anti-anemia medications or JAK inhibitors; ruxolitinib for symptomatic spleen or general symptoms. We are looking later this year to have similar NCCN guidelines in place for patients with ET and PV.
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