Lengthy piece of research and I need to try to understand certain aspects better. It discusses impact of Inf on high risk mutations plus impact of multiple mutations re progression to AML. Of interest to Steve, INF reduces high risk mutations such as ASLX1 to same level as other non Driver mutations
Concludes that INF is beneficial re slowing progression of MF but sting in the tail is that increases risk of severe/fatal GVHD if then opting for SCT. The $m question is how long pre SCT must one stop INF or does any use of INF raise post SCT GVHD risk?
Not sure about any of claims that this article might make...?
At the present, all I can view from your link is a single page .jpeg file that promotes a comparative table of sorts.
Paul, do you have an actual link to the complete article so we can also check for any 'Conflict of Interests?'
Often, the manufacturers of these drugs are also the company paying for these types of article/s to be published, which one must in turn view with some suspicion, in my view...
When such things occur, I do not believe that we should pay too much kudos to those papers, as their findings may be flawed in some respect.
Usually, 'Declared Interests', are noted toward the end of these types of papers/articles.
Steve, In this case there are no conflict of interests in this peer-reviewed article, funded by the French Cancer Institute. Dr Kiladjian (lead author) is a leading French MPN expert, that has published widely on interferon outcomes. I find his articles some of the clearest and easiest to read for the non-medical audiences! Susana
Great article Paul, thanks for sharing. I have been on Pegasys for almost 3 years for PV, with great success. There is limited evidence on the effects of Pegasys on advanced myelofibrosis so very helpful to see the results of this encouraging study by Dr Kiladjian and colleagues. It was surprising that the reduction in mutational burden had no effect whatsoever on survival and disease transformation, as also found in a recent Dr Silver study - the significance of the allele burden is still very unclear, which is probably why it is not routinely measured on the NHS. And it is the first time I read about the link between interferon treatment and stem cell transplant outcomes, although the number of patients undergoing SCT was small so would be good to see more research on this link. Thanks again for posting. Susana x
You say the reduction in Allele Burden had no effect on survival and progression? I must re-read the article since I thought Interferon reduced likelihood of additional mutations, nullified the poor prognosis of the high risk mutations to same label as additional non driver mutations and significantly increased survival?
Have I missed a part where some people had a poor outcome despite reducing AB?
My take on high AB (I’m 75% AB and PV) is that it increases my risk of developing additional mutations. Hence if I’m prone to additional mutations, high AB will load the dice a bit rather than direct correlation with progression. Like Steve, I’m heavily into anti inflammatory diet since hopefully improves the odds against secondary mutations/cancers.
Interesting that those who tolerated Interferon well benefited the most. Good news for you after 3 years!
- ‘We did not observe any difference of outcome (death or acute myeloid leukemia evolution) between patients whose JAK2V617F allele burden did or did not decrease’ (Evolution of allele burden)
- ‘the reduction of the JAK2V617F allele burden did not have any impact on overall survival or leukemia-free survival in our study. Silver et al. also recently reported such an absence of correlation between molecular response and clinical outcomes in a series of 30 myelofibrosis patients treated with interferon’ (Discussion)
My own view is that lowering the AB has to be a good thing at some level, even though these small scale studies might not pick up a statistically significant effect!
I’m still confused by exactly what your quote implies?
The report concludes that INF prolongs life, reduces impact of high risk mutations and reduces new mutations. This all implies slowing progression?
The critical take away is that our ability to tolerate INF equates to its efficacy re our individual prognosis.
IMO we can’t conclude that high AB irrelevant, rather that if we can tolerate it, INF allows us to possibly live longer despite the increased risk of a high AB?
Have you read about our, imo, best short term hope drug - RG7388? In Phase 2 trials now. Basically the angle is that MPN patients at risk of their MDM2 gene being overactive and suppressing p53 from combating new mutations/cancers. RG7388 targets MDM2, freeing up p53. My understanding from various presentations is that a high AB stimulates MDM2 to some extent.
For me, the rather unnerving conclusion from reading this report is that there is a dearth of reliable clinical data and to some extent our Hems are learning as they go along. The good news is that they are learning fast, judging by the pipeline of new drugs.
Hi Paul, Certainly there is plenty of evidence that interferon works and slows progression, and this article is also very positive about its efficacy - which is indeed the main lesson here and great news for those of us that are on Pegasys! There is also evidence that interferon reduces the allele burden. It is the precise role and prognostic significance of the 'allele burden' that is not known, as I understand it. My haemo said they don't measure it routinely in the UK as currently, knowing what it is it does not change prognosis or treatment. As a result, I have no idea what mine is!
I read about the RG7388 drug in relation to AML. Sounds promising. It is fortunate for us that there is active on-going research on blood cancers, including gene editing research. And I agree with you: our haemos are learning fast. We have come a long way since 2005 and the discovery of the Jak2 mutation.
Thank you first for the updated link, and yes it worked just fine...
Okay, I have now had my first scan, and it appears to be quite an interesting study indeed. I will over time go back over it, a few more times cross-referencing as I go, because, as it turns out the authors cite many of the papers I am already somewhat familiar with.
Once again Paul, thank you so much for your efforts, and for sharing them with all of us here...
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Disposal of unused Pegasys Interferon
Change from Interferon to Pegasys 
Starting low dose Interferon Pegasys 
