Rampal: The major point I would say is that using genomics is now a standard of care and it is fundamental to the care of patients with myelofibrosis. We need to go beyond just looking for JAK1/2 mutations; we need to look at all the other mutations available. That gives us a sense of prognosis.
I would encourage physicians to think about repeating genomic testing during a patient’s course because we know that genomics can evolve, but we don’t always test for genomic evolution. The reason for that is that we may say at one point that a patient looks relatively low risk, but genetically, their disease may evolve and change the patient’s risk. Even though things might seem stable, clinically, in terms of blood counts, there may be a genomic evolution going on that could be an early warning that the disease itself is going to progress and transform.
Other than considering a transplant, what are the advantages of knowing your prognosis? Besides possibly treatment dose? or using INF over HU? or fast tracking to Rux or doing quite the opposite of that?I ask because I genuinely don’t know and I think there is more I’m unaware of and I myself have not bothered to have in depth gene analysis. I think I’d rather not know and keep my quality of sanity…not you, Hunter?
Hunter, do you know if Cindy has posted her updated?
The way I experience it is that knowledge is power. I feel empowered by knowing more about the factors that determine my health status and the knowledge helps to shape my decisions.
When it appeared my MPN might be progressing due to the uptick in thrombocytosis (by 200K) I rechecked the JAK2 allele burden and did the MPN Myeloid NGS panel to look for non-driver mutations. The MAB only increased by 1% and the only non-driver mutation present was NF1, which I already knew that I had. We concluded the uptick in thrombocytosis was due to the iron deficiency, not disease progression. This allowed me to make decisions about next steps for treatment, but to also know I could take my time reviewing my options.
Ultimately the knowledge of my genomic status was an important part of choosing to begin Pegasys. While my MPN has been slow to progress, I am at elevated risk for progression to AML due to the NF1 mutation. I chose PEG since the IFNs offer the best chance of current options to prevent disease progression. PEG-IFN also offers a good chance for better symptom control, which is the primary goal of all of my treatment choices.
Thinking more long-term, genomics research will allow more tailored treatment decisions for MPNs based on the individual genetic profile. This is the direction that much cancer research is moving in. It would be a significant step forward to be able to determine which treatment an individual was most likely to benefit from rather than rely on trial and error. The number of treatment options we have is expanding. It may double in the next 10 years. Hopefully genomics will help to guide treatment decisions going forward.
Thanks Hunter. I had allele burden check 18 month ago and thought that was it. This shows that we will have to insist on it being done more often, ie every few years?. I thought good blood counts were sufficient evidence of stable condition but apparently not. So after 16 years of PV I need to be more aware of ways to see progression. Thanks again.
The thinking on this is emerging. How we think about and use genomic information is becoming more sophisticated and informative. Dr. John Mascarenhas addressed this in the presentation he did today. (I believe the Which MPN Treatment is Right for You? webinar will be posted for those who missed it).
At this point, my own approach to retesting for allele burden is to do it when there is a reason to. A change in apparent disease status would be a reason to. Due to the clonal advantage of JAK2 mutated hemopoietic stem cells progression of allele burden is likely to occur. It will often occur quite slowly until it does not. At this point I would not check every year since I know my MAB only increased by 1% from 2018-2019. I may recheck in several years of being on PEGylate interferon to see if the MAB has reduced as it is a relevant marker of treatment efficacy. Molecular remission would be a good thing and relevant to ongoing treatment decisions. Of course we will be monitoring for hematologic remission as well.
There is also the issue of non-driver mutations. This is relevant at the outset of treatment. It allows for risk stratification and can shape treatment decisions. In addition, everyone acquires 20 - 24 new mutations in every year of life. Most of these are silent. If one of the mutations is a non-driver MPN risk factor then it could result in progression of a MPN that has otherwise been stable. At this point, rechecking when you have a reason to makes sense to me. Perhaps routinely checking at point of diagnosis and then at intervals thereafter will become the standard of care. I certainly think that it should be the standard of care for MPNs.
The genomics research is a significant step forward in MPN care. I believe it will allow for more tailored and effective treatment in the future. I would say that the future begins now. There is genomic testing available now. There are MPN specialists who are using this information in clinical practice already. The are patients who are advocating for this to be considered as a part of their MPN care. That is both our right and our responsibility.
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SCT while feeling well
Waiting for diagnosis: ET or Pre-pmf
Specialist 2nd visit 
