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Symptoms, Diagnosis, and QoL in Patients With Myelofibrosis

Panelists: Harry Erba, MD, PhD, Duke Cancer Institute; John Mascarenhas, MD, Icahn School of Medicine at Mount Sinai; Mary Francis McMullin, MD, Queen's University Belfast; Robyn Scherber, MD, UT Health San Antonio MD Anderson Cancer Center; Moshe Talpaz, MD, University of Michigan Health System
Published: Friday, Feb 14, 2020



Transcript:

Harry Erba, MD, PhD: Let’s switch gears and spend most of the remaining time—not all of it, but most of it—on myelofibrosis. It’s clearly a clinical challenge for physicians out there and their patients. Dr Robyn Scherber, I’m going to start with you. I’m taking advantage of your work looking at symptoms and the MTM [medication therapy management]. Why don’t you tell us how patients with MF [myelofibrosis] present?

Robyn Scherber, MD: I think early on, John did a great job of really explaining what happens with the blood count, especially in PDT [photodynamic therapy], where you’re seeing very red count and platelets. in early stages you can still see that high red blood cell count and potentially in high platelets, but you start to see the white blood cell count go up. Over time you actually start to see the cytopenias starting to come in, especially thrombocytopenia and anemia. That really is what clues us in. We also see our markers of inflammation go up, especially CRP [C-reactive protein], start to climb up. From a patient’s perspective, we’re shown that the symptoms are also a key thing that go up when you go into myelofibrosis. Quite interestingly in ET [essential thrombocythemia], PV [polycythemia vera], and MF and start to subsequently increase in terms of symptom burden.

The No. 1 symptom patients present with is fatigue. You also get a lot of constitutional symptoms, especially fevers and night sweats. Those can go up. Abdominal symptoms because of the increased frequencies of splenomegaly. Early satiety, abdominal discomfort. The other key symptom we see with this is weight loss in some patients, and when we do start to see that, we know that can be an adverse prognostic indicator.

These are all things to be aware of in new patients to be monitoring over time. One key thing we see is incorporated in NCCN [National Comprehensive Cancer Network] Guidelines and in our practice is that we want to not only get a baseline effect from the symptoms but see how they’re changing over time.

Harry Erba, MD, PhD: One of the challenges is that a lot of our patients tell us they’re fatigued, and usually the doctor in the rolls their eyes and is like, “Me too.” It’s really hard to actually measure that. They may say fatigue, but then you ask them what they’re during the day, and they actually haven’t cut back on anything. It’s a real event in their lives that they could tell the difference. Any clues that you can give, Mary Frances, about to sort through this very important symptom?

Mary Frances McMullin, MD: Well, there’s the scoring. This is a huge difficulty, and certainly our recent patients. There are patients who are so eloquent about this fatigue, that this is different from being tired at the end of the day. I was very impressed listening to them, how different it is from what we mean by fatigue.

I think that to try to measure it is difficult. The MFIS is probably the most useful thing, and you can do that scoring and repeatedly score patients as they come through the clinic. That’s what we would aspire to, although there are lots of issues about how you get that done and where you store the results and what happens to the results and keeping the whole thing going. At least it gives you some sort of a measure for the patients. It’s something you can repeat if you give them therapy and see if there is a difference.

Harry Erba, MD, PhD: Just to remind the group, when we first embarked on the development of JAK inhibitors, we knew this was a drug that affected—or we believe affected—cytokines, which mediate symptoms. We embarked on trying to figure out how to quantify that. One of the things we used early on, which I distinctly remember prior to the advent of ruxolitinib, is the 6-minute-walk test. We would have the patients walk back and forth 6 minutes, and that was somehow a gait. I realize now it’s totally useless, but at that point that was the technology that we used to try to gauge whether someone's overall performance status and their energy level and fatigue was improving. It’s clearly not an effective way.

Robyn Scherber, MD: One thing I will say about symptoms is that we’ve recently done an interesting analysis of the COMFORT studies. We have seen that symptoms actually can be predictive of survival. The other thing is even just overall quality of life in MF patients and at baseline was predictive of overall survival. That’s something to really keep mind with MF patients as well as all your MPN [myeloproliferative neoplasms] patients. A lot of times, because this chronic malignancy is really key to our treatments of them, when we’re deciding what treatment to give and how to best manage them, we need to make sure their quality of life is teed up.

Mary Frances McMullin, MD: The other thing that was interesting was the where we had controls and we did the MFS 10 on the patients on the controls. Much to the delight of the patients, they scored much worse on the symptoms than controls. It’s more than just, “I’m tired.”

Harry Erba, MD, PhD: It’s an important issue, and it drives a lot of our decision making in treating this disease. I’m going to come back to your comments about ruxolitinib and fatigue and quality of life and how it might lead to survival too. We’ll come back to that. Mary Frances, tell us about how we make this diagnosis of that.

Mary Frances McMullin, MD: The patients present with a history examination, and splenomegaly is what you’re looking for. Everybody has tales of patients who are referred with a mask, which is actually the spleen. You would then want to quantify measure the spleen. We would do an ultrasound, maybe a CT [computed tomography] scan or an MRI [magnetic resonance imaging] depending on the process. I would want them to look at a blood film, in particular look at the blood counts. First, looking for anemia, then thrombocytopenia, and the blood film for the presence of teardrop cells. Teardrop cells have to be seen because we’re making a diagnosis of myelofibrosis. Then these patients of course all need a bone marrow done because you need the bone marrow to see the fibrosis. I think we’re now in the age of molecular testing. Obviously JAK2, MPL, and CALR but also more expensive molecular testing, looking for other mutations that feed into the prognosis and the prognostication.

Transcript Edited for Clarity

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Transcript:

Harry Erba, MD, PhD: Let’s switch gears and spend most of the remaining time—not all of it, but most of it—on myelofibrosis. It’s clearly a clinical challenge for physicians out there and their patients. Dr Robyn Scherber, I’m going to start with you. I’m taking advantage of your work looking at symptoms and the MTM [medication therapy management]. Why don’t you tell us how patients with MF [myelofibrosis] present?

Robyn Scherber, MD: I think early on, John did a great job of really explaining what happens with the blood count, especially in PDT [photodynamic therapy], where you’re seeing very red count and platelets. in early stages you can still see that high red blood cell count and potentially in high platelets, but you start to see the white blood cell count go up. Over time you actually start to see the cytopenias starting to come in, especially thrombocytopenia and anemia. That really is what clues us in. We also see our markers of inflammation go up, especially CRP [C-reactive protein], start to climb up. From a patient’s perspective, we’re shown that the symptoms are also a key thing that go up when you go into myelofibrosis. Quite interestingly in ET [essential thrombocythemia], PV [polycythemia vera], and MF and start to subsequently increase in terms of symptom burden.

The No. 1 symptom patients present with is fatigue. You also get a lot of constitutional symptoms, especially fevers and night sweats. Those can go up. Abdominal symptoms because of the increased frequencies of splenomegaly. Early satiety, abdominal discomfort. The other key symptom we see with this is weight loss in some patients, and when we do start to see that, we know that can be an adverse prognostic indicator.

These are all things to be aware of in new patients to be monitoring over time. One key thing we see is incorporated in NCCN [National Comprehensive Cancer Network] Guidelines and in our practice is that we want to not only get a baseline effect from the symptoms but see how they’re changing over time.

Harry Erba, MD, PhD: One of the challenges is that a lot of our patients tell us they’re fatigued, and usually the doctor in the rolls their eyes and is like, “Me too.” It’s really hard to actually measure that. They may say fatigue, but then you ask them what they’re during the day, and they actually haven’t cut back on anything. It’s a real event in their lives that they could tell the difference. Any clues that you can give, Mary Frances, about to sort through this very important symptom?

Mary Frances McMullin, MD: Well, there’s the scoring. This is a huge difficulty, and certainly our recent patients. There are patients who are so eloquent about this fatigue, that this is different from being tired at the end of the day. I was very impressed listening to them, how different it is from what we mean by fatigue.

I think that to try to measure it is difficult. The MFIS is probably the most useful thing, and you can do that scoring and repeatedly score patients as they come through the clinic. That’s what we would aspire to, although there are lots of issues about how you get that done and where you store the results and what happens to the results and keeping the whole thing going. At least it gives you some sort of a measure for the patients. It’s something you can repeat if you give them therapy and see if there is a difference.

Harry Erba, MD, PhD: Just to remind the group, when we first embarked on the development of JAK inhibitors, we knew this was a drug that affected—or we believe affected—cytokines, which mediate symptoms. We embarked on trying to figure out how to quantify that. One of the things we used early on, which I distinctly remember prior to the advent of ruxolitinib, is the 6-minute-walk test. We would have the patients walk back and forth 6 minutes, and that was somehow a gait. I realize now it’s totally useless, but at that point that was the technology that we used to try to gauge whether someone's overall performance status and their energy level and fatigue was improving. It’s clearly not an effective way.

Robyn Scherber, MD: One thing I will say about symptoms is that we’ve recently done an interesting analysis of the COMFORT studies. We have seen that symptoms actually can be predictive of survival. The other thing is even just overall quality of life in MF patients and at baseline was predictive of overall survival. That’s something to really keep mind with MF patients as well as all your MPN [myeloproliferative neoplasms] patients. A lot of times, because this chronic malignancy is really key to our treatments of them, when we’re deciding what treatment to give and how to best manage them, we need to make sure their quality of life is teed up.

Mary Frances McMullin, MD: The other thing that was interesting was the where we had controls and we did the MFS 10 on the patients on the controls. Much to the delight of the patients, they scored much worse on the symptoms than controls. It’s more than just, “I’m tired.”

Harry Erba, MD, PhD: It’s an important issue, and it drives a lot of our decision making in treating this disease. I’m going to come back to your comments about ruxolitinib and fatigue and quality of life and how it might lead to survival too. We’ll come back to that. Mary Frances, tell us about how we make this diagnosis of that.

Mary Frances McMullin, MD: The patients present with a history examination, and splenomegaly is what you’re looking for. Everybody has tales of patients who are referred with a mask, which is actually the spleen. You would then want to quantify measure the spleen. We would do an ultrasound, maybe a CT [computed tomography] scan or an MRI [magnetic resonance imaging] depending on the process. I would want them to look at a blood film, in particular look at the blood counts. First, looking for anemia, then thrombocytopenia, and the blood film for the presence of teardrop cells. Teardrop cells have to be seen because we’re making a diagnosis of myelofibrosis. Then these patients of course all need a bone marrow done because you need the bone marrow to see the fibrosis. I think we’re now in the age of molecular testing. Obviously JAK2, MPL, and CALR but also more expensive molecular testing, looking for other mutations that feed into the prognosis and the prognostication.

Transcript Edited for Clarity
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