Diagnosis and Prognosis of Primary Myelofibrosis

Ruben Mesa, MD, FACP: Hello, and welcome to this OncLive® Peer Exchange® program on the updates and the management of myeloproliferative neoplasms. I’m Ruben Mesa. I am the executive director of the Mays Cancer Center at UT Health San Antonio MD Anderson Cancer Center. I’m joined by 3 wonderful MPN [myeloproliferative neoplasm] experts and good friends for this discussion today. First, I’m going to introduce Professor Jamile Shammo from Rush University in Chicago, Illinois. Welcome.

Jamile Shammo, MD, FASCP, FACP: Thank you, Ruben.

Ruben Mesa, MD, FACP: Next, we have Pankit Vachhani from the University of Alabama at Birmingham (UAB).

Pankit Vachhani, MD: Thank you.

Ruben Mesa, MD, FACP: We also have my good friend and fellow Texan Dr Srdan Verstovsek.

Srdan Verstovsek, MD, PhD: Hello, Ruben. Hello, everybody.

Ruben Mesa, MD, FACP: We’re going to have a discussion, first about myelofibrosis, then about polycythemia vera. Patients with myelofibrosis are quite heterogenous. It’s amazing what a mix this disease can be for individuals. Jamile, why don’t you walk us through how we think about risk and burden for these patients with myelofibrosis?

Jamile Shammo, MD, FASCP, FACP: Everybody would agree that risk assessment is so important to identify those who have low vs high risk. Anybody who’s taking care of those patients would have to be familiar with the prognostic scheme that looks at various clinical variables associated with overall survival. You have the IPSS [International Prognostic Symptom Score], you have the Dynamic International Prognostic Scoring System [DIPSS], and you have something called an enhanced prognostic scoring system. Those encompass variable clinical parameters that we all have to be familiar with, so you can concoct the score and say whether your patient is low risk or high risk. Clearly, high-risk patients must be considered for transplantation and those who have lower-risk disease—we can talk about the role of transplanting for this particular group. It’s extremely important because the survival rate for this group of patients varies. If you look at low-risk patients, the IPSS should be performed at diagnosis. You are looking at 11 years of overall survival vs the highest score possible, which is 2 years. That’s a huge difference if you look at the DIPSS Plus, which encompasses things like cytogenetics or platelet count. If there are poor cytogenetics, you’re looking at 15 years vs 2 years. That’s a huge difference. We need to become familiar with those prognostic schemes.

Ruben Mesa, MD, FACP: That’svery helpful. We know that some of the molecular markers are increasingly woven into some of these scores. Pankit, in your practice at UAB, you’re also on the NCCN [National Comprehensive Cancer Network] panel. Srdan and I had been on that group in the past. It rotated as things evolved. Where do you use those new NGS [next generation sequencing] panels? Where does NCCN suggest we do them for patients with myelofibrosis?

Pankit Vachhani, MD: At present, we at UAB—and at most academic medical centers—use NGS panels at the time of diagnosis for patients who have myelofibrosis. With the typical risk-scoring stratification—IPSS, DIPSS, DIPSS Plus—that’s not incorporated into decision-making in the initial stats. However, we do get prognostic value out of those comprehensive NGS panels. For example, fine mutations like EZH2, ASXL1, and SRSF2, or the IDH1, IDH2 mutations are high risk in nature for progression. This comes into play most when you’re dealing with patients with intermediate-1 risk myelofibrosis, when you’re wondering if you should send them to transplant early. That’s an additional piece of information that you can get to risk stratify. On the other hand, if you were using a DIPSS or an IPSS risk-scoring stratification, that would be crucial over there as well.

Ruben Mesa, MD, FACP: That’s very helpful. As I sit with patients, this discussion of risk and prognosis is important. It’s a very heterogeneous disease. Indeed, individuals can have very short- or long-lived disease. I’m also very mindful of the concept of their symptoms as part of the burden they face. Do they have splenomegaly? Do they have symptoms of splenomegaly? Many of the constitutional symptoms we can now question them about using the standardized questionnaires that my team—with many collaborators’ help—developed. We can determine whether that’s a baseline, how that evolves, and how that impacts therapy.

Transcript Edited for Clarity