Practical Risk Assessment in Myelofibrosis

Transcript:Kim-Hien T. Dao, DO, PhD: The Dynamic International Prognostic Scoring System (DIPSS) was developed to help providers assign risk groups according to various characteristics associated with myelofibrosis. This includes their age, leukocytosis, hemoglobin value, peripheral blast count, and constitutional symptoms, like weight loss, night sweats, and fevers. Using this system, we can categorize patients into low-, intermediate-, or high-risk groups. And based on that, a provider may be able to develop an individualized monitoring and treatment plan to manage these patients.

There are key markers of rapidly progressing disease, and these are things that I screen for and also educate my patients to look for in between visits. These include escalating symptoms, development of new low blood counts that are progressive, and also splenomegaly. So, these are things that a provider can look for to indicate, perhaps, that the disease is progressing.

Daniel J. DeAngelo, MD, PhD: Patients with myelofibrosis present in various stages of their disease, and this has been quantitated based on, initially, the International Working Group (IWG) prognostic scoring system, the same way we look at patients with myelodysplasia, which we’ve been doing for two decades now. The IWG Prognostic Scoring System, which was published by Cervantes a number of years ago, really only stratified patients at the time of their diagnosis. They looked at criteria, at the initial presentation, including age, white count—either high, low—anemia, and patients with circulating blasts and constitutional symptoms—again, a very important feature. Unfortunately, this was not validated in terms of following patients throughout their course. The dynamic, or DIPSS as it’s called, was then developed to follow patients throughout their course to reassess patients to see whether there’s a clinical progression.

And what came out of that, in addition to those factors that were initially identified by Cervantes and his group, by the IWG, was the degree of anemia. And so, patients who develop progressive anemia are patients who are indicative of having a more rapid decline. Putting a quantitative number on a scoring system is fine as long as you know what scoring system can be used when. But, a little bit of clinical acumen, I think, is important. You know a patient is ill when you see them. The performance status is obviously a key.

My clinical judgment is when patients are having rapidly progressive splenic enlargement, number 1. Number 2, patients are rapidly increasing their peripheral blast count. The most predictive of progressive disease, in my opinion, in addition to those two objectives, is the subjective assessment of constitutional symptoms, specifically looking at weight loss and early satiety. It seems to be this catch-22, or issue, that patients develop. Once they start losing weight, they really rapidly deteriorate. And I find that that’s a big clue and really should be a point of when to intervene therapeutically.

Srdan Verstovsek, MD, PhD: Risk assessment in myelofibrosis is very important. We have tools that we have developed. These are international prognostic scoring systems that can be applicable at the time of diagnosis or at any time during the disease course. One is called IPSS and the other one is called Dynamic IPSS, which are very useful to us as the risk of dying of the patients based on past experience. Of course, this needs to be taken with a little bit of reservation because we do have therapies at this point in time, like ruxolitinib, that are proven to improve the longevity of the patients. So, the outcome of the patients that we treat now is, by default, improved by our availability of new therapy that improves the survival. But, nevertheless, knowing what is the perceived projection of life expectancy of the patient is important, particularly for a referral to a bone marrow transplant. Younger and fit patients that have more aggressive disease based on prognostication, intermediate 2 and high-risk patients, should be referred for a bone marrow transplant. And the younger ones, and fit patients, that perhaps don’t have such aggressive disease—based on the standard prognostication—but have genetic complexity that we can test for now—perhaps triple negative disease that do not have any of the driver mutations like the JAK2, MPL, or calreticulin or can have some other additional bad prognostic mutations—should be considered for early transplant.

The other reason for prognostication is also implementation of a therapy. In the United States, ruxolitinib is indicated for patients with intermediate and high risk, which does make sense. The low-risk patients are those that don’t have a big spleen, don’t have symptoms, don’t have advanced age, don’t have anemia, and don’t have any clinically relevant problems with the disease.

Transcript Edited for Clarity