Nikolai Podoltsev, MD, PhD, associate professor of medicine (hematology) at the Yale School of Medicine, New Haven, Connecticut, shares key insights from his session on managing myelofibrosis at ASH 2023 and looks at some of the exciting research on the horizon.

Transcript:

Nikolai Podoltsev, MD, PhD: My name is Dr Nikolai Podoltsev. I'm an associate professor of medicine in the hematology section at the Yale School of Medicine.

Can you please summarize some of the recent updates in myelofibrosis treatment as discussed in your session at ASH 2023 titled “Optimizing Myelofibrosis Management With Current and Emerging Therapies”? 

Dr Podoltsev: This was an education session during satellite symposia CME session organized by Medscape. And, as you pointed out, it was about optimizing management of myelofibrosis.

This session was organized because now we have 4 JAK inhibitors which are in use for patients with myelofibrosis, and the whole purpose of it was to figure out how to use these medications since the fourth one was just approved. Momelotinib was just approved in September of 2023.

What were some of your highlights from the session? 

Dr Podoltsev: Overall the addition of more medications for this group of patients, which are quite difficult to manage, is welcomed. And the medications are from the same class of JAK inhibitors, but nevertheless, they have different mechanisms of action which allow us to understand better how to differentially use them in different sets of patients.

So we have ruxolitinib, which is available since 2011, when it was approved by FDA for patients with intermediate and high-risk myelofibrosis. Then fedratinib joined ruxolitinib with 2019 approved for intermediate to and high-risk myelofibrosis patients as based on the IPSS. And in 2022 pacritinib was added to the list, and finally, in 2023, in September, momelotinib.

Are there any promising emerging therapies or ongoing clinical trials in the field of myelofibrosis that you find particularly intriguing or that you believe may have a significant impact on future treatment approaches?

You know, there are a number of studies. I just want to highlight a couple. So the hot topic in the field is using of doublets. So in addition to ruxolitinib, which is well-accepted frontline treatment for most of the patients. Should we add another medication to ruxolitinib to make it perhaps more effective, maybe the combination will be disease modifying. And there are a couple of presentations attached in 2023, which deserve our attention, including MANIFEST-2 study, which is a phase 3 trial looking at ruxolitinib with pelabresib versus ruxolitinib and placebo, as well as TRANSFORM-1 study, with ruxolitinib and venetoclax versus ruxolitinib versus placebo. Both studies met primary endpoint of spleen reduction, and there were some differences in responses related to symptom control.

And you know there are a number of studies which are looking at additional doublets, including ruxolitinib plus selinexor, the phase 3 trial which we're hoping to open soon. Another study I would like to highlight is ongoing phase 3 trial of imetelstat in patients with relapsed, refractory disease. These are patients who progress and didn't or didn't respond to frontline JAK inhibitor therapy with exciting endpoint overall survival.

How do you ensure that your treatment plans are aligned with the individual needs and preferences of your patients with myelofibrosis? Can you provide an example of a case where you tailored the treatment approach to accommodate a patient’s specific circumstances or preferences?

Dr Podoltsev: I highlighted my approach during the education session we started this conversation about, at ASH. I'm using an acronym, which is PASS: P.A.S.S. And PASS letters stand for something, so P is prognosis, A is for anemia/thrombocytopenia, S is for systemic symptoms, and the second S is for spleen and spleen-related symptoms.

So this acronym allows me to use systematic approach with each patient newly diagnosed with myelofibrosis, and helps me to educate fellows how to do this. So for prognosis in patients with primary myelofibrosis, I'm using MIPSS70+ version 2.0 prognostic scoring system, and MYSEC-PM for patients who have secondary, post PT, post EV myelofibrosis.

The application of this model allows us to project a median overall survival of these patients. And if it is short, basically, if expected, survival is less than 5 years, I would consider referring this patient's phylogenetic stem cell transplant. Next part of the acronym is A, which stands for anemia, and not to forget thrombocytopenia. So anemia requires management, and also can affect similar to thrombocytopenia, how we approach management of systemic and spleen-related symptoms.

There are few treatment options for anemia itself, including erythropoiesis-stimulating agents for those who have erythropoietin level less than 500, but also some other drugs, which are in development, including luspatercept, currently being studied together with ruxolitinib in INDEPENDENCE, phase 3 INDEPENDENCE study.

The momelotinib, the JAK inhibitor, which I've mentioned most recently approved one is also indicated by FDA for patients with symptoms and anemia, and will be appropriate for patients who have lower hemoglobins.

Finally, thrombocytopenia is an issue for some of the patients, and there are no treatments we currently have to fix the platelet count, but we can certainly use pacritinib, the drug which is approved for patients with platelet count less than 50 if we need symptom control in those patients who have thrombocytopenia.

Certainly there are more options now specifically for patients with anemia and thrombocytopenia. In regard to systemic symptoms and spleen-related symptoms, the ruxolitinib, and perhaps fedratinib the most effective ways of controlling the symptoms, but taking into consideration anemia and thrombocytopenia, we may consider using momelotinib and pacritinib, respectively. This is how I apply it to a patient, and I did see a patient with newly, not with newly diagnosed myelofibrosis. This patient came to see me for second opinion. He did have diagnosis of primary myelofibrosis, established a few years ago, and initially was treated with ruxolitinib. Unfortunately, he developed severe anemia and thrombocytopenia, and ruxolitinib had to be discontinued.

So then he was on prednisone for symptom control, and pacritinib was requested by his provider, but was not approved. Eventually, when patient came to see me, his platelet count was actually normalized, and hemoglobin remained around 10. He did have significant symptoms when I saw him last week, and my suggestion was to use momelotinib, which may be gentle for anemia and actually improve it, but also we’ll have to control symptoms in a patient who previously was on ruxolitinib.