Tag Archive for: DIPSS

When Should Myelofibrosis Mutational Testing Be Repeated?

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When should myelofibrosis mutational testing be repeated? Dr. Pemmaraju discusses the importance of retesting at key points and how mutations impact care and treatment plans. 

Dr. Naveen Pemmaraju is Director of the Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) Program and Professor in the Department of Leukemia at The University of Texas MD Anderson Cancer Center. Learn more about Dr. Pemmaraju.

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Transcript:

Katherine Banwell:

“I understand that mutational testing should be done at diagnosis. Is there a point where there would be a need to repeat this test?”  

Dr. Naveen Pemmaraju:

Oh, that’s an awesome question. So, we were mentioning that earlier. I do believe and I advocate that all patients should have molecular testing, particularly now as it’s more available widely before it wasn’t. Again, we level set what we’re talking about. In myelofibrosis, three common driver mutations, JAK2, CALR, MPL makes up about 90 percent. 

Then in addition to that, there’s the triple-negative, and you usually find an additional mutation. Then on top of these big three, it’s common to have co-mutations, ASXL1, etc. What we found in this MIPSS score that we just mentioned ties into that. We found now that for the first time, we can incorporate these molecular findings to prognosticate for the patients. That’s why it’s important to check them. So, to this question by Joel, yes, if you have access and availability, not only checking it at baseline but later on at a provoking event.  

So, at the time of relapse, progression, going onto a clinical trial, just to name three of several. I think it’s a good idea to recheck the molecular status. The problem and barriers are what you would expect, cost, expense, access, availability, justification, etc., etc. So, it’s not a mandatory part of the field, especially in the standard of care, non-research aspect. However, if we can get to the point where we can do that, it would be nice and helpful because these mutations change, they’re dynamic.   

You can have negative for mutation at baseline, positive, and even vice versa, depending on therapies. Are you going to go for a transplant? Are you going to go to a clinical trial? Are you changing therapy? It would be nice to know. 

How Are Prognostic Scoring Systems Used in Myelofibrosis Care?

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How are scoring systems such as DIPSS used in myelofibrosis care? Dr. Pemmaraju explains how these tools assess myelofibrosis prognosis and guide treatment decisions. 

Dr. Naveen Pemmaraju is Director of the Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) Program and Professor in the Department of Leukemia at The University of Texas MD Anderson Cancer Center. Learn more about Dr. Pemmaraju.

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Myelofibrosis Care | The Impact of Test Results

Transcript:

Katherine Banwell:

“Can you explain the dynamic international prognostic scoring system or DIPSS?” Thank goodness there’s an acronym for that.  

Dr. Naveen Pemmaraju:

Yeah, no, it’s a great question, scoring systems, right?  

Katherine Banwell:

Yeah, and Cliff wants to know how he can ask his doctor about it.  

Dr. Naveen Pemmaraju:

Right, so the easiest way to talk about it, the good news is everything we’ve been talking about is incorporated in the scoring system. So, said in another way, we’ve been talking about it subjectively, the scoring systems try to make the subject objective. So, quick history, these started in 2009 with the IPSS, International Prognostic Scoring System. The concept there were a thousand patients in Europe and basically trying to observe the natural history of the progression of myelofibrosis. This was just before, just as the JAK inhibitor era was starting. What we found is that the four groups nicely separate.  

So, the lowest of the low-risk group potentially can be measured in decades for overall survival. Intermediate one, intermediate two, and high risk, again, all separated by overall survival and AML leukemia transformation risk. Now, that’s evolved over time as the questioner is asking for more sophisticated scoring systems. So, that’s all you need to know. So, DIPSS Plus just means Dynamic International Prognostic Scoring System.  

Then there’s DIPSS plus, and can you believe it? There’s even the MIPSS now, the Molecular International Prognostic Scoring System. All right. So, at least there’s a rhyme and reason there. I think each iteration is telling you that we are dynamically understanding more about the disease. Two, the IPSS, the original one, was meant to be only at diagnosis, and the DIPSS by definition, dynamic scoring, is any time during the course of the disease, that’s interesting. Then three, they’re incorporating new factors each time.   

So, from the time of the IPSS to the DIPSS and now the MIPSS, you’re incorporating all these factors that we couldn’t before. Cytogenetics, molecular findings, anemia, transfusion, burn, thrombocytopenia, etc. So, that’s basically it. You can ask your doctor. I mean, basically, in the course of what we do in the non-clinical trial standard of care, even if somebody doesn’t hand stop and calculate these risk scores, we’re talking about the same thing, right? The subjective or the objective matchup.  

However, of interest to the patients, there are calculators that are available, you know, obviously rather than doing it in isolation in your house. Yes, it is better, I agree to do it with your doctor, with your provider team, and see what it means for you. The goal of these is twofold. In clinical trials to help stratify patients so you can understand who’s high risk versus lower. However, in the standard of care, sure it may help with transplant decisions, referrals for clinical trials, etc. 

How Does Risk Stratification Shape Myelofibrosis Treatment?

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What is involved in determining low risk versus high risk myelofibrosis? Expert Dr. Michael Grunwald from Levine Cancer Institute discusses IPSS, DIPSS, MYSEC-PM, and MIPSS70 scoring systems, key patient factors they weigh in determining risk, and why risk stratification is an essential part of myelofibrosis care. 

[ACT]IVATION TIP

“…risk stratification is important because it can impact treatment choices including whether to initiate treatment, whether to pursue transplantation, and sometimes the type of treatment as well. Also, lower risk patients can require treatment at times for symptoms and splenomegaly in myelofibrosis.”

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Transcript:

Lisa Hatfield:

Dr. Grunwald, what is lower risk versus higher risk myelofibrosis?

Dr. Michael Grunwald:

Fortunately, we have various risk stratification systems available. We have the International Prognostic Scoring System or IPSS, and then later on, the Dynamic International Prognostic Scoring System or DIPSS scoring system was developed to risk stratify patients. And then the DIPSS Plus, there’s the MYSEC-PM scoring system, which is specifically for patients who have a history of essential thrombocythemia or ET, or polycythemia vera or PV, who then developed myelofibrosis.

And then finally, we have the Molecular Scoring Systems, the Molecular International Prognostic Scoring System, which is called the MIPSS70. And then the newest one of those is the MIPSS70 Plus version 2.0. So we have a lot of different risk stratification systems and they have many features in common.

These risk stratification systems look at patient’s age, their blood counts, sometimes whether patients are so anemic that they’re requiring blood transfusions, the percentage of blasts in the peripheral blood, the degree of fibrosis or scar tissue in the bone marrow, their cytogenetics. So whether patients are missing big chunks of genes in their bone marrow or whether chunks of genes are translocated from one chromosome to another chromosome.

And then finally, the Molecular Scoring Systems take into account individual genetic mutations. Based on these features of a patient’s disease, we can determine whether a patient is at high or low risk of progression and also high or low risk of mortality from myelofibrosis. And the scoring systems are all a little bit different, so it’s confusing, but there are certain features that are common among low risk patients. So more normal blood counts, lower percentages of blasts in the peripheral blood, less fibrosis in the bone marrow, and then more favorable mutations, which could be chromosomal abnormalities or individual genetic mutations. Higher risk patients tend to have more abnormal blood counts, higher blast percentages, more fibrosis in the marrow, and then unfavorable risk mutations.

And from this we get a sense of whether a patient’s disease is likely to progress to acute leukemia, and also whether a patient is at risk of death from myelofibrosis in the near future. This information can be very helpful because it can guide us in our recommendations for treatment or sometimes for no treatment for a patient.

Lisa Hatfield:

Ok, thank you. So if I were your patient and I was just recently diagnosed with myelofibrosis and I said I heard that I was staged or given the risk stratification from the DIPSS system, would you know what that means and how that might relate to other systems of staging or do I need to be aware myself that it means this, that it means I am lower risk or higher risk, will you tell me that if I was sitting in your office?

Dr. Michael Grunwald:

Yes. So I went through this with patients yesterday where we sat together and we looked at the scoring systems, and we looked at a few of the scoring systems, and we plugged in patients’ numbers into scoring system calculators that are available online. So I can plug in the white count, I can plug in the patient’s platelet count, their hemoglobin, their mutations, and figure out what their DIPSS score is, what their DIPSS Plus score is, what their MIPSS70 score is. And I like it when the information from the different scoring systems is fairly concordant.

For example, if a patient is low risk by all of the risk stratification systems, makes me very confident that a patient is low risk. And then if there’s more discordance where, let’s say, a patient has a molecular mutation that indicates high risk and heavily sways the MIPSS70 or MIPSS70 Plus version 2.0 toward the higher end of the risk spectrum, and we have another scoring system, one of the older ones that would indicate lower risk, that’s where the conversation is a little bit more difficult. And I tend to trust the newer molecular systems a little more, especially in patients who had no previous history of essential thrombocythemia (ET) or polycythemia vera (PV). And we do discuss that with the patients, both the clinical attributes and the genetic attributes of the disease.

My [ACT]IVATION tip for this question is, risk stratification is important because it can impact treatment choices including whether to initiate treatment, whether to pursue transplantation, and sometimes the type of treatment as well. Also, lower risk patients can require treatment at times for symptoms and splenomegaly in myelofibrosis.

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When Should Stem Cell Transplants Be Considered for MPN Treatment?

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When Should Stem Cell Transplants Be Considered for MPN Treatment?  from Patient Empowerment Network on Vimeo.

Dr. Jeanne Palmer, an MPN specialist, discusses when a stem cell transplant is an appropriate treatment option and provides an overview of how risk is assessed in MPN patients. 

Dr. Jeanne Palmer is a hematologist specializing in myeloproliferative neoplasms (MPNs) and bone marrow transplant at the Mayo Clinic in Arizona. Dr. Palmer also serves as Director of the Blood and Marrow Transplant Program and is Vice Chair and Section Chief for Hematology. Learn more about Dr. Palmer, here.

 

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Transcript:

Katherine Banwell:

When would you consider a stem cell transplant? 

Dr. Jeanne Palmer:

So, the stem cell transplant is based on disease risk. There is a number of ways we assess disease risk.  

The first two ones that were published a number of years back were the DIPSS score, which is Dynamic International Prognostic System Score, or the DIPSS Plus, which basically is the DIPSS and then you add to it a few other clinical features. This symptom score is based largely on things that we can see without even a bone marrow biopsy, so things like symptoms, age, number of white blood cells, whether somebody has anemia. And then the number of something called blasts, which is very immature white blood cells. The DIPSS Plus takes into account low platelets, need for transfusions, and chromosome abnormalities, which is the only test among that that needs to be from a bone marrow biopsy. 

Now, these were created prior to Jakafi being commercially available. So, we have to take a little bit of a grain of salt with those because of the fact that Jakafi probably has changed how long people can live with this disease. 

Now, more recently they’ve tried to account for these other molecular changes. So, when we take the genetic landscape of these diseases, we have the known driver mutations, so the JAK2 mutation which I have talked about, also calreticulin and MPL.  

These three mutations all affect that one pathway, the JAK/STAT pathway, so they all affect the pathway that drives the disease and they are known to be kind of mutually exclusive and definitely contribute to the formation of the disease. 

Some of these other mutations are called somatic mutations. They could be checked by things next generation sequencing or genetic analysis. There’s a number of different names that people use for this testing, but we look for mutations that are present and these mutations, number one, can sometimes tell us risk. So, there’s certain mutations that are high risk. Other times it can actually give us other opportunities for therapy, especially of the disease progresses. But these mutations are important to know for risk stratification. For example, if somebody has DIPSS score that is maybe not super high risk, but then they have one of these mutations, we know that that probably makes their disease a little bit more aggressive. 

And that’s when we think about transplant, is when we know that the disease probably has an average life – when somebody gets to the point in their disease where we estimate their life expectancy is around five years, recognizing that we’re not very good at this. That is the type of point when we start to think about transplant. But the timing of transplant is something that’s extremely difficult and a very personalized decision. It’s something that it’s really important to understand the disease risks, how we assess them and the caveats of these disease risk assessments as we move forward planning and timing of transplant and that’s something that is, again, a very, very important discussion to have at length with your physician. 

And I always recommend, there is quite a few of us out there who actually specialize in transplant for myelofibrosis and having discussions with somebody who really understands the biology of the myelofibrosis is important because it’s very different than a lot of the other diseases that are transplanted. 

What Questions Should Patients Ask About MPN Test Results?

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What Questions Should Patients Ask About MPN Test Results? from Patient Empowerment Network on Vimeo.

What should you know about your MPN test results? Dr. Mascarenhas discusses how test results are used, including the importance of genetic mutations and risk stratification when analyzing results.

Dr. John Mascarenhas is Associate Professor of Medicine at the Icahn School of Medicine at Mount Sinai (ISMMS) and the Director of the Adult Leukemia Program and Leader of Clinical Investigation within the Myeloproliferative Disorders Program at Mount Sinai. Learn more about Dr. Mascarenhas, here.

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Transcript

Katherine Banwell: 

Some patients may not know if they’ve received these important tests. So, what key questions should they ask their physician about testing?

Dr. Mascarenhas:       

Well, I think it’s important that the patients feel empowered to understand sort of where the field is and what key questions you would ask a physician, hematologist who’s taking care of you. So, I think all patients should be aware of their diagnosis, the name of the diagnosis, the subtype, but also do they have any of the key driving mutations, the JAK2 mutation, the calreticulin mutation, the MPL mutation, and that’s usually done off of a bone marrow biopsy sample, but it can be done off peripheral blood. And, they may not always know that it’s done. So, I think having a discussion with the position to understand there are criteria that exist called the World Health Organization criteria that are updated frequently and should set a standard throughout the world of how you diagnose and establish these diagnoses.

So, I think it’s important for physicians to be able to convey to the patients with confidence, “We follow these criteria and you have these criteria and we’ve done this testing that shows that you have these mutations.” And not just regurgitate what they found, but help them understand and navigate with that means, which again, I will point out that sometimes we don’t know. But, I think it’s important for physicians to convey sometimes that some of the findings that they may see, for example, patients look on portals these days and they can look at their labs and stuff like that. And, we don’t always have a terrific answer or an informed answer for everything that we get back. And, we will potentially in 10 years from now, but sometimes at the moment, we don’t. But, I think a discussion about the meaning of the labs that are obtained is probably good for the patient to understand what’s being done.

Katherine Ba:nwell:

Absolutely. It sounds like each person’s situation is unique and should be considered before making any treatment choices. Can you talk about how the results of these tests may affect prognosis and treatment?

Dr. Mascarenhas:     

So, we do have risk stratification systems that we use for essential thrombocythemia, polycythemia vera, and myelofibrosis. I’ll talk about myelofibrosis because that’s probably a little bit more of a complex and sophisticated model. It’s also changing, and we update it frequently. And, these models are imperfect, so I always warn patients to not put all of their money in one basket when we talk about risk stratification. They broadly help us understand where a patient is in their disease course. So, for example, in myelofibrosis, historically, the DIPSS, the Dynamic International Prognostic Scoring System is used, which considered five clinical variables that have been shown to be independently prognostic. So, at age over 65, the presence of blasts or circulating immature cells in the peripheral blood, anemia, hemoglobin less than 10, symptoms, fevers, night sweats, weight loss or a high white count over 25,000, you those points up.

And patients can do this online. There are calculators that you can calculate your DIPSS score. And, you’ll see that there are four different risk groups that range from low risk to high risk, and they are associated with median survivals. We now know that mutations influence those, have influence on prognosis. So, there are a group of high molecular risk mutations like ASXL1, SRSF2, IDH1/2. So, there are mutations that also have prognostic significance, and we incorporate them into the decision-making.

And, essentially, and this is where I think patients have to be very careful, physicians have to be very careful with conveying this. With these risk models whether they are clinical variable risk models or these integrated molecular risk models, each category is associated with a median survival, that’s based on retrospective studies. But that doesn’t tell the patient specifically what they should expect in terms of survival. And, I always fear that patients, when they look at these things, or even physicians when they convey them that they may inadvertently misrepresent or convey what those really mean.

And, I think the purpose of those risk stratifications is really to help guide a risk adapted treatment approach that’s reasonable and is weighted for benefit to risk of the disease. So, for example, if you have advanced disease with a high-risk score of intermediate to or higher, bone marrow transplant in certain patients may be a warranted therapy to consider. So, they really help inform treatment.