Case 1: Risk Stratification Models for Myelofibrosis

Rami Komrakji, MD: Once we established the diagnosis, our next step is risk stratification because we are going to tailor the treatment based on that. In myelofibrosis over the past few years, there have been several models that have evolved in risk stratification. Some of them are purely clinical, and some of the newer models incorporate some of the molecular and genetic material within the risk stratification. The classical models have been the IPSS, the International Prognostic Scoring System, or the Dynamic IPSS or the Dynamic IPSS-Plus. All of those will weigh on tentative factors such as patient age, anemia, leukocytosis, and presence of blasts—constitutional symptoms. Some of them, in addition, like the DIPSS will allow for the model weighing on the anemia and the blood cell transfusion. The DIPSS-Plus will account for the thrombocytopenia as well as the karyotype. We can generally divide patients into 4 risk groups, from low, intermediate-1, intermediate-2, to highest, and the median survival that is according to those risk groups, from somewhere between 1 to 2 years for somebody who is labeled as a high risk, to someone that has a median overall survival exceeding 10 years if they are low risk.

So our patient, she’s above the age of 65, she’s anemic, has leukocytosis, some constitutional symptoms, and the platelets are below 100, she’s definitely going to be at higher risk using the IPSS or DIPSS-Plus.

In certain cases also as I mentioned, nowadays, we have some molecular models. There is the genetically inspired prognostic scoring system, or the MIPSS70, that had evolved particularly to allow risk stratification for patients we are considering for allogeneic stem-cell transplant, because it’s geared for those patients at the age that we think of transplant. It does not count the age as a risk factor. It incorporates presence of molecular mutations, whether the patient has calreticulin mutation or not, other high-risk mutations defined by presence of ASXL1, EZH2, SRSF2, or IDH1 or IDH2, and the newer version is actually also related to AF mutation as well. So based on clinical variables and molecule variables, we would put the patients in 1 out of 3 risk groups, the low, intermediate, or high, and the survival of these 3 will vary based on that group. If we take our patient here again, she probably would be high risk with the clinical variables and incorporating the absence of the calreticulin mutation and the bone marrow fibrosis.

There is another model that’s used mostly or primarily for patients for post-ET [essential thrombocythemia] or post-PV [polycythemia vera] myelofibrosis. This is the MYSEC Prognostic Model that was particularly developed in a cohort of patients that had secondary myelofibrosis. So this is myelofibrosis from either essential thrombocythemia or polycythemia vera. We see here the variables used there are the age, hemoglobin level, platelets, presence of circulating blasts, the calreticulin mutation status, as well as constitutional symptoms, and we can divide patients into 4 groups based on that. This model is available online and one can plug in the numbers and see the outcome for the patients nicely with that model.

Transcript edited for clarity.