Primary Myelofibrosis: Risk Stratification

Harry P. Erba, MD, PhD: We can continue to talk about polycythemia vera for quite some time, which is different from 10 years ago, or maybe 20 years ago, even before the JAK2 variant was found in PV.

However, it’s time to move on, and I’m going to ask Jamile to start with a discussion of patient classification and risk stratification in myelofibrosis. For the sake of time, we will not spend a lot of time on the diagnostic criteria, which are well-published by the WHO and will move on to risk stratification and how that affects management of patients. Jamile?

Jamile M. Shammo, MD, FASCP, FACP: There are multiple prognostic scoring schema that have been developed over the years. The first was published in 2009 by Cervantes, and it’s called the IPSS [International Prognostic Scoring System], which was a tool utilized at the time of diagnosis to risk stratify patients relative to their survival. There were 5 variables that were utilized: age over 65, white blood cell count over 25,000 per mm3, peripheral blast count over 1%, presence of constitutional symptoms, and hemoglobin below 10 g/dL.

That gave you 4 risk groups with median overall survival ranging from 130-some months down to 27 months, so you can see a tremendous variation of variability. In general, people think low-risk to INT-1 [intermediate-1 risk] is lumped together as 1 entity and then INT-2 and high-risk disease as another.

Mostly, stem cell transplant patients were offered to intermediate- and high-risk disease, but it then became clear that, as people went on to live with this disorder, they acquired other features that may also correlate with worse outcomes, namely the development of anemia transfusion and transfusion dependence. This is why the Dynamic International Prognostic Scoring System [DIPSS] was created to account for the development of anemia in patients who may not have been at the outset.

That was the next advance, and later, the DIPSS plus also accounted for a few other variables, including the platelet count below 100,000 per mm3, the presence of adverse cytogenetic abnormalities, and the development of transfusion dependency. The bottom line is that, whichever score you utilize, remember that the IPSS is good for the time of diagnosis, and the dynamic scores are good throughout the disease scores.

When the mutations became available with JAK2, MPL, and CALR, people started to look at the impact of those mutations on the outcome of patients who had myelofibrosis. There was a trend to think to include those mutations into the scoring schema, so there’s something called mutation-enhanced international prognostic scoring system [MIPSS70], which encompasses the presence of certain mutations that are labeled as high risk. That evolved into the MIPSS70-plus, which includes cytogenetic abnormalities.

All that culminated in the genetically inspired prognostic scoring system, and that includes both molecular and cytogenetic abnormalities. I know this is a lot of information, and all the little bullets that you have in there to construct a scoring schema are interesting, and it may help in selecting people who may be candidates for stem cell transplant patients. I will stop there.

Harry P. Erba, MD, PhD: Thanks, Jamile. That was an excellent summary, because it has evolved and now includes the mutational and cytogenetic data, which are prognostically important.

Transcript Edited for Clarity