Harry P. Erba, MD, PhD: Jamie, let’s come back to that question about intervention for intermediate and high-risk patients versus low-risk or asymptomatic patients. We all know we see the 66-year-old with 2% blasts 1 day, and right then, that would make that patient intermediate-2: a candidate for ruxolitinib or fedratinib, the 2 FDA-approved agents. However, they’re completely asymptomatic, or at least they tell you so. We can ask Ruben to comment on whether that’s true if they’re completely asymptomatic.

Let’s say you have somebody who is happy with their quality of life, and they’re 66 years old, and they have 2% blasts 1 day or they have a sweat every 3 months. They’ve made it to the intermediate-risk group. Do you rush to put all those patients on therapy? What kind of conversation do you have with patients about that?

Jamile M. Shammo, MD, FASCP, FACP: It’s a question, Harry, because it’s a commitment when you start a patient with myelofibrosis on ruxolitinib. There is a lot of blood testing that you have to do, there is follow-up, and there is a lot more that they need to do. They have to be convinced that they are in need of added treatment.

Your point about making sure that we have totally validated their symptoms in some kind of measure, as opposed to just, “Yeah, I’m feeling fine,” is extremely important. What about their spleens? Have they grown larger over time? Those questions are all important. There are a couple of studies, even though the initial COMFORT studies, which I know Srdan will talk about, looked at intermediate-2 and high-risk disease.

There are some data to support the use of ruxolitinib in some intermediate-1 patients that have splenomegaly or symptomatology. We have to be flexible in understanding each patient and think of other symptoms they are dealing with: Do they justify the initiation of treatment that will require frequent monitoring? Once they start, they’re set to continue, right? It’s a conversation we need to have with the patient.

Harry P. Erba, MD, PhD: Yeah, and sometimes I don’t convince my patients. I clearly have intermediate-risk patients, and after talking with them and looking at their family, I say “This patient is symptomatic,” and the patient says, “I don’t want to start a chronic medication yet.” It’s the fun part about being a doctor.

Ruben, let’s come back to NCCN Guidelines. What is recommended for the intermediate- and high-risk patients? How do you choose between these? We’ll then get into the clinical data.

Ruben A. Mesa, MD, FACP: Excellent. The guidelines are certainly based on the most broadly used risk score. We talk about intermediate and high risk by which criteria? Those have still been based off the DIPSS, which are the most broadly available and used criteria, but it does bring up some other more granular issues in prognosis that Jamile had brought up.

For intermedaite-1-risk patients, they have a heterogenous prognosis because we realize that some of those might be young individuals with anemia and a high-risk molecular mutation that by MIPSS70 might be much more high risk. But by DIPSS, they might still be intermediate-1.

The full gamut exists under the NCCN Guidelines from JAK inhibition for splenomegaly and symptoms to allogeneic transplant for people who might be higher risk, to even just observation if they were intermediate-1 solely on the basis of age. That was probably the most mixed group. If your patient falls in the intermediate-1, I strongly advise physicians—particularly of patients of transplantable age—to get an NGS panel to further clarify their prognosis.

For intermediate-2 and high-risk patients, that is your most standard group. That is the largest group of patients with MF. That initial decision is this: Do you consider transplant in the near term? Building on that discussion you had with Krisstina regarding who the candidates are, anyone who says that it’s an easy decision is not the person facing the transplant.

Comparing a transplant with medical therapy is comparing 2 different animals altogether. It’s different both philosophically and in terms of scope. The frontline medical therapy includes ruxolitinib, which has been the frontline therapy for many years, but it now also fedratinib under the NCCN Guidelines since September 2019.

JAK inhibition is used with the goal of improving spleen, symptoms, and aspects of the disease. Importantly, we then have to monitor for efficacy and decide on whether frontline therapy has had sufficient efficacy. Or one considers perhaps switching from 1 of those agents to another or alternative approaches.

Transcript Edited for Clarity