The New Era of Treating Myelofibrosis - Episode 1
Srdan Verstovsek, MD, PhD, describes the classic signs and symptoms of primary myelofibrosis (PMF), along with goals of therapy.
Srdan Verstovsek, MD, PhD: Primary myelofibrosis has different signs and symptoms, but the 3 classic ones are, No. 1, bone marrow failure that represents itself with anemia in particular. No. 1 is the anemia. The second one is the symptomatic splenomegaly. In about 80% of patients, a big spleen develops. In about 40% of patients, a big liver develops, and they become symptomatic. Symptomatic splenomegaly is the No. 2 factor. Lastly, the No. 3 factor is general bad quality of life. I’m talking about systemic myelofibrosis-related symptoms: night sweating, low-grade fevers, fatigue, itching, weakness, body wasting, decreased performance status, bone aches and pains. Thus, these are parts of the disease spectrum that we are talking about, anemia, symptomatic splenomegaly, and general bad quality of life. Those are the 3 leading problems and 3 leading reasons for trying different therapies to counteract those signs and symptoms of myelofibrosis in everyday practice.
Once we establish the diagnosis of myelofibrosis, the next question is what’s the risk? The risk that we are talking about is the risk of dying. There are prognostic factors that can be used to assess the risk of dying. The primary goal is to say, who has a life expectancy of less than 5 years, and to refer those patients to a bone marrow transplant department and try to save the life of the patients with that relatively invasive procedure. For those who have a life expectancy of more than 5 years, we don’t do that, because the transplant is risky on its own. Once we are done with prognostication, we move on to identify symptoms and signs that require therapy. If there are no significant symptoms and signs, for example, no significant anemia, no significant symptomatic splenomegaly, or no significant issue with quality of life, then sometimes we observe the patient. The low-risk patients usually are like that. We may observe them. As they progress through life with the disease, they become high risk because they develop anemia and the symptoms, for example, these are their prognostic factors. There is overlap between the risk of dying prematurely and the initiation of therapy. For the lower risk therefore, we would occasionally need therapy, and occasionally treat patients for symptomatic splenomegaly, or bad quality of life. Or occasionally for some other reasons, like very high platelets, or very high white blood cell count, to decrease this myeloid proliferation. For high-risk patients, we certainly would treat the patients, and this is where symptom burden comes in. Symptomatic splenomegaly, or general systemic symptoms, are 2 out of the 3 major problems. Also, it is many times tied to the risk of dying. Thus, standard practice would be, if the patient is symptomatic, occasionally in low-risk patients, but normally present in high-risk patients, to utilize the JAK inhibitors. We have a couple of JAK inhibitors, ruxolitinib and fedratinib, that are approved as a therapy for patients who are symptomatic, and who are intermediate or high risk. One or the other are listed in national guidelines as a choice.
Transcript Edited for Clarity