Jamile M. Shammo, MD, FASCP, FACP: I think it’s been reported that 30% of patients who have myelofibrosis may actually be asymptomatic. Ultimately, nearly everybody is going to develop symptoms, either related to anemia, fatigue, or splenomegaly, and constitutional symptoms. I try to understand the phenotype of the patient. Anemia obviously requires looking at the serum erythropoietin level and considering ESAs [erythropoiesis-stimulating agents] for someone who may have an endogenous level below 125. Then if there’s no response after 8 to 12 weeks, perhaps you move on to alternate agents such as immune modulators, danazol, and hopefully, clinical trials afterward if there’s no response.

For those who have splenomegaly, severe constitutional symptoms, and perhaps anemia mixed in with that, JAK [Janus kinase] inhibitors represent a very reasonable frontline therapy. This was driven from the data that came from the COMFORT trial. When do I switch treatment? Well, there have been some descriptions of relapse, or intolerance, or resistance, if you will, to initial JAK inhibitor therapy such as ruxolitinib. Then, obviously, with ruxolitinib being the only FDA-approved agent, I would consider putting those patients who had not responded, or adequately responded, on to a clinical trial.

Harry P. Erba, MD, PhD: Ruben, clearly we’ve been talking about, other than transplant as the only curative option, palliation. You have to have some way of measuring palliation. This has been a real focus of your clinical investigation and research. Can you help us with how clinicians should be evaluating patients, in terms of symptom burden, and also response to therapy?

Ruben A. Mesa, MD, FACP: Sure. First, I would frame it as really about trying to alleviate the burden that patients with myelofibrosis face. I’d say that palliation is sometimes used incorrectly, in almost a pejorative way, that it’s not having a real impact on the patient. In myelofibrosis, for many patients, they will have survivals that can range from a handful of years to many years, from the time of diagnosis. That burden of disease, as we’ve been alluding to, is symptom burden. It’s spleen-related difficulties, potential cytopenias, and there is that risk of progression and mortality. All of the risks come in to that piece, and the timing of transplant.

The medical therapy that we have clearly has a genuine impact, not only on the days of life lived. For a patient who is benefiting from medical therapy with ruxolitinib or another disease-related therapy, if it’s efficacious, they are living longer. They may not be cured, but they are living longer. It is impacting the disease, as well as the burden of the disease.

Now, the burden of the disease is very important to both assess and then track, because it’s helpful not only in terms of assessing the utilization of therapy, but adjusting dose, as well as determining whether the therapy is efficacious. We’ve learned many things as we’ve walked this arc and now have data in thousands of patients with myelofibrosis. We have similar data that are comparable across most of the studies that now are done in myelofibrosis, which is very helpful.

There are different portfolios of spleen-related symptoms. There can be pain, discomfort, early satiety, and a range that are tied to that piece. There are clearly cytokine-driven symptoms that relate to cachexia, fatigue, pruritis, and night sweats, etcetera. Then there are other symptoms that clearly may be associated with the most progressive end of the disease. Bone pain and fever, which are really the most uncommon. People boil it down and say, “What are some of the most impactful?” One of the most impactful is really pathologic weight loss. It is such an aberrant feature in our society. Nobody loses weight without trying. We all know this well.

If patients are, that is a big red flag in my eyes that something is out of balance with the disease. That’s also something that we do note as a pretty strong marker of response to JAK inhibition. That part is both arrested or reversed. The takeaways I would have for people listening to this, it’s very important, and not only in clinical trials, it’s very important in terms of monitoring the disease.

These tools are now readily available. People should fill them out in the lobby. As you examine the patient and their spleen size, and as you’re looking at their blood counts, you look at what their symptom profile is. Is that the same, better, or worse? If it’s still not where you would like it to be, is there an opportunity for increasing the dose of your JAK inhibition? If they have been stable for 2 years and now it’s clearly worse, is that a sign of a new comorbidity? I found that has sometimes been the case, patients have developed a different disease. They’re now eligible for a clinical trial for progressive disease, or things of that nature. So, 1), medical therapy is having an impact on the patients, and 2), you really need to be monitoring that serially to adequately manage the patient.

Transcript Edited for Clarity