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When Should an MPN Patient Retest for Genetic Mutations?

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Published on March 16, 2021

How Often Should Patients Undergo Genetic Testing?

At what points in time should an MPN patient be retested to verify their diagnosis and check for changes in their mutation profile? Dr. Naval Daver, MD, Associate Professor in the Department of Leukemia at MD Anderson Cancer Center, explains the optimal times to test to properly treat myeloproliferative neoplasms, especially during a change of status or progression of the disease.

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Transcript | When Should an MPN Patient Retest for Genetic Mutations?

Dr. Daver: Hello. My name is Naval Daver, I am a faculty in the Department of Leukemia at the MD Anderson Cancer Center in Houston, Texas. I focus on clinical trials in myeloid malignancies, and it's a pleasure to speak to you today. I'm going to be talking about the optimal testing in the current era for patients with myeloproliferative neoplasms, and what are the time points to consider repeat testing, whether it's molecular cytogenetic to know if there are changes in the status of the disease. So there has been a lot of progress in the understanding of the molecular landscape, as well as the chromosome landscape of myelofibrosis, especially. And we do know a number of mutations now that can be frequently seen in patients with myelofibrosis, including JAK2, MPL, calreticulin. These are what we call the JAK-STAT activating mutations that are very typically seen in about 60% to 70% of the myelofibrosis patients. 

When Do Changes to an MPN Patient’s Genetic Profile Typically Occur?

However, now we also know that there are other mutations that can be seen, especially at the time of transformation or progression of myelofibrosis to accelerated phase or blast phase myelofibrosis. So more rapid progressive disease that usually needs to be treated more aggressively. And those mutations that occur when the myelofibrosis is transitioning from the chronic, slow-growing to the aggressive more proliferative accelerated blast phase are mutations like IDH1, IDH2, TP53. And these are very important mutations to look for if there is any concern or clinical signs or symptoms or bone marrow changes that are suspicious for blast or accelerated phase because there are targetable drugs that can target these mutations for IDH1, for IDH2 and even potentially for TP53. So, we usually do bone marrows every one to two years in our primary myelofibrosis patients. We are looking for the traditional JAK-STAT mutations, but also these other mutations IDH1, IDH2, TP53, to see if there's any acquisition or emergence of these mutations that could help us use targeted therapies down the line.

Can Genetic Mutations Have an Impact on Prognosis?

There are other mutations like ASXL1, for example, which has been associated with a relatively adverse outcome and a higher risk of transformation when present. These are not yet mutations that we necessarily act on therapeutically. It's not clear whether we could change the prognostic impact of these mutations with therapies, but these do have prognostic impact. And if I have a younger patient who has primary myelofibrosis and ASXL1 with some splenomegaly and symptoms, I may be a little bit more inclined toward thinking about early intervention such as stem cell transplant. Again, not standard of care, but a lot of us are thinking along these lines because we do know some of these mutations could have an adverse outcome.

So I think again, important to look for those additional mutations, both at diagnosis, more importantly, at the time of transformation or progression, which could have a therapeutic decision-making, give options for targeted therapies which usually have the best chance of success, and also may push us towards the earlier or more proactive stem cell transplant in certain patients where we know the risk is higher because of certain mutations that they have.