Heterogeneity of Therapy in Patients With MPNs

Ruben Mesa, MD, and Jamile M. Shammo, MD, discuss available treatment options, such as JAK inhibitors, and the goals of treatment for patients with MPNs.

Bruce Feinberg, DO: Ruben, a lot of patients struggle, or it could be a struggle in caring for them, because they are not necessarily symptomatic. I see both sides of that coin. They have an abnormality of a laboratory test that produces some risk to them, but they do not necessarily feel it. I am curious about your perspective on the fact that a lot of patients are asymptomatic or minimally symptomatic because that often has a big impact on the goals of treatment and the compliance with treatment. Give me your perspective.

Ruben Mesa, MD: As we have done a lot of collaborative, symptom-based research in these patients over the years, I would say probably three-fourths of patients have symptoms for their MPNs [myeloproliferative neoplasms]. Part of the challenge with patients with MPNs has been that, for many, particularly practicing US medical oncologists, they may be the least sick looking person they see that day. If the person before them has advanced ovarian cancer, and the subsequent patient has pancreatic cancer, your patient with ET [essential thrombocythemia] is going to look pretty healthy, but they do have symptoms.

I have not found compliance to be a challenge, but with a condition like this, No 1, the discussion that Michael and Kathy have brought up is important. The quality standards for these patients in terms of trying to appropriately manage them is key. Educating the patient regarding the goals of care, what we are monitoring, and what to watch for with the disease is an important part. I was the inaugural panel chair for the NCCN [National Comprehensive Cancer Network] guidelines for MPNs, and part of it was to help inform this quality discussion. Care in the United States was still quite heterogeneous, in part because people were bringing whatever they had, or what they most recently remembered from their training, to their practice for patients with MPNs. As to what the target was or what drug to use, it was incredibly heterogeneous. For many patients, this meant that they were probably being undertreated to be honest. That has been a journey.

I would like to see how value-based care in cancer has been evolving from the intensive cyclical solid tumor chemotherapy focus to now with many more of these long-term chronic states. I too am a cancer center director [at The University of Texas Health San Antonio MD Anderson Cancer Center], and I think in these terms. You have the people who have gotten 4 months of intensive interactive therapy with your infusion unit, but you also have a whole other group of folks who have a very chronic illness: bone-only metastatic breast cancer, optimally debulked ovarian cancer, follicular lymphoma, MGUS [monoclonal gammopathy of undetermined significance], MPNs, low-grade MDS [myelodysplastic syndrome]. It goes on and on; these are people who have years of a much more chronic course of disease, but bringing those same lessons we learned in intensive cases to chronic disease management is important.

Bruce Feinberg, DO: Right. It is interesting. As you go over that list, you can now add things like metastatic melanoma. That is how things are changing over time, and it is fascinating. This echoes all the points that Michael and Kathy were making about consistency in the way that you are approaching these patients. You talked about the heterogeneity of therapy, but you did not talk about all the different therapeutic options that might be considered. With an audience that may be less familiar, the only thing they may know about is JAK inhibitors. Heterogeneous therapy suggests there are a lot of options. What is in the armamentarium that can be used? Let’s start with you, Dr Mesa, and we will then move to Jamile to get her thoughts on it.

Ruben Mesa, MD: Perfect. Let me divide it into the 2 major groups: earlier MPNs and later MPNs. Earlier MPNs are ET and PV [polycythemia vera], for which the goals of therapy are to make the disease as invisible in the life of the patient as possible: prevention of blood clots and bleeding, control of symptoms if present, and maybe ideally in the future, avoidance of progression. For this, we believe that most individuals benefit from a baby aspirin, both in ET and PV. In polycythemia vera, we aim to control of the hematocrit level, possibly with a strict hematocrit control of under 45% through phlebotomy.

In individuals who also can receive cytoreductive therapy, it matters if they are higher risk, if they do not tolerate the more conservative approach, if they are older, if they have cardiovascular risks, if they have symptoms. If they are not doing great with the other approach, then we add cytoreductive therapy, which might include hydroxyurea or long-acting interferons. Both of those are frontline options in the NCCN guidelines, with ruxolitinib as second-line therapy for polycythemia vera.

With myelofibrosis [MF], the situation is different. The disease is more life-threatening; there is a much higher rate of challenges with symptoms, such as significant splenomegaly and sometimes cytopenias. For these individuals, we first decide between observation, stem cell transplantation for more aggressive disease in younger individuals, or medical therapy, of which 2 JAK inhibitors, ruxolitinib and fedratinib, are approved as frontline therapies that can impact splenomegaly symptoms, and they have a largely favorable impact on survival.

Bruce Feinberg, DO: Jamile, that was a pretty comprehensive discussion. Would you add or subtract anything?

Jamile M. Shammo, MD: I wholeheartedly agree. The only other thing I would add is that there is another option being considered for patients who have polycythemia, which is called ropeginterferon. It is a form of interferon that may be added to the treatment armamentarium for patients who have polycythemia. It is being considered by the FDA, so it will be interesting to see if that may get added to what we offer patients who have PV.

Of course, that is not something we could do for MF, although there have been some clinical trials in patents with MF with interferons, but those patients are generally treated with JAK inhibitors, and there are essentially 2 JAK inhibitors that are available for patients who have this. Of course, there are a whole slew of clinical trials for patients who have this disease, which is something that we typically end up relying on because none of those treatments are curative.

Transcript edited for clarity.

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