I have seen some people write that this drug does not have much effect on calr AB,it can control the platelets count, but it May have no effects on AB percentage
So is there any chance for calr ET patients to have remission with this drug?and is it necessary to have max dose of it to achieve mullecular remission?
I think the jury is still out on the impact of the interferons on CALR allele burden. I think you are right though about what seems to be the case. Regarding dose, common sense would indicate that a higher dose would reduce AB more, but I have not seen any clear evidence that points to that outcome. I think it make the most sense to take the smallest dose needed for a complete hematologic response and hope for the best. The the IFNs do have dose-dependant side effects. They are not a whole lot of fun.
Hi and thank you so much for your information .Honestly i agree with you about choosing minimum needed dose because of its effects on liver.Although we can check up liver enzymes by routine blood test but liver disease is something so weird and it can gradually start without any signs (the only way to be sure about it is sonogram not blood test)so as you said we can just hope for the best🙌🏼
Hi I’m Calr and on Peg, I don’t know my allele burden. I did ask about it once but the heamo didn’t even have it. I might ask for clarification at my next appointment. 🥴if I remember lol
I have read several medical journals that show molecular remission is possible with CALR mutation.
Here’s one for example:
pubmed.ncbi.nlm.nih.gov/264...
I’ve seen several studies on people who take ifn for 3-5 years and then experience long term remission >5yrs after coming off of it.
You're correct, in a prior post this report was discussed:
ncbi.nlm.nih.gov/pmc/articl...
<<In contrast, the CALR variant allele frequency did not significantly decline in those achieving CHR or in those not achieving CHR (complete hematologic response )>>
This figure shows it graphically for INF. The blue box in Fig. A for Jak2 is consistently lowered while the blue box in B for CALR is not much lower than the red one. But both Jak2 and CALR seem similar, and not too good, for no-CHR.
*But* this went for only 24 months. As noted by dbus1417 above, longer treatment is beneficial, as is common with INF. Also this report included pre and MF patients where results are likely to differ from ET only.
This study also addresses a consistent finding I'm seeing, that CHR relates to AB reductions in general at least for Jak 2.
This report also points to CHR for all relating to lower odds of non-driver mutations.
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In future good news, a very fresh report on Bomedemstat shows it having effect on CALR AB, mean of 29%. . So this drug may be of help here, but it's only in phase 2 trials now.
library.ehaweb.org/eha/2022...
<<,JAK2 and CALR mutations were equally sensitive: 87% had a decrease in allele frequencies (mean: -29%;>> Also <<No new mutations were found.>> This is a better result than the INF/HU study above where new mutations were found in some.
Thank you so much for this helpful text so am i right that even with calr mutations if we achieve CHR probably MR is possible??
In general it seems there is more data on Jak 2 than CALR, possibly bec Jak2 is the largest portion of MPN patients. Getting consistent info on CALR seems more difficult.
There are reports that CALR MR can respond well to INF. There are conflicting reports regarding the effect of CALR type (type 1 vs type 2) I recently posted as below.
Even the term CALR Type is getting out of date as they find more "types".
See my reply to joetcalr here with opposing findings:
healthunlocked.com/mpnvoice...
Non-driver mutations are relevant:<<we observed a poorer MR rate on CALR mutant clones in patients harboring additional mutations>> This same effect is seen with Jak2.
If I were CALR I would try to know which type I had in case it proves important, and get next gen sequencing esp for future reference. I had early next gen gene test for my Jak2.
Hi, that’s a great question. I started on interferon nearly a year ago and at my last consultation my doctor after the appointment in his clinic letter said that I had Complete haematological remission. I’ve been on 45mg every two weeks. So this is something I will discuss with him in a few weeks when I am back. He did an allele burden test as a base line when we started which was 40%
I agree with your question on Max dose. It is an unresolved question right now with my specialist.
I recently posted details on this, see link. With this info my opinion is we should take enough INF to hold CHR, and CHR correlates well to MR. With this info, we should not just keep going blind to what's happening inside us. I'm not sure my Dr is in agreement here.
One of the charts in this post also uses allele burden along with CHR as part of the feedback. But none propose to just keep on adding dose to an arbitrary number.
These are only my opinions.
healthunlocked.com/mpnvoice...
« It has been found that even low doses of IFNα were effective in targeting homozygous JAK2V617F HSCs, however, high doses (> 100 µg/week) were needed for heterozygous JAK2V617F HSCs. IFNα was least effective in targeting heterozygous CALR-mutated HSCs »mpn-hub.com/medical-informa...
Neat reference. It's consistent with what we've been seeing regarding the homozy Jak2.
They separate mature blood alleles from immature progenitors, which I think is one part of the marrow. There must be another sort of marrow allele since blood and marrow AB are usually similar. My guess is once the marrow cells with allele mature they are equivalent to blood cells and these are what we usually see in our AB tests.
They define CMR as 100% reduction. (I assume to limit of detection) I didn't know that was possible. 5% of jak2s got there in the blood.
<< low doses of IFNα were effective in targeting homozygous JAK2V617F HSCs...high doses (> 100 µg/week) were needed for heterozygous JAK2V617F HSCs.>> Big question is whether these responses tracked CHR, the other reports I've posted suggest they should. But it's more evidence we should have our Jak2 -zygous status tested.
For CALR the blood allele actually had better 100% MR results. But generally inferior results vs Jak2. It would be interesting if they had separated by CALR type. It's possible a subset had a good response. But one bar, for CD34, 38+, had zero 100% responses; this stands out and does suggest something different with CALR.
Jak2 treatment was almost a year longer than CALR, could be that had some effect on the difference. Like so many reports, we don't get to see the fine data or plots.
Hi EPguy,You wrote : « They define CMR as 100% reduction. (I assume to limit of detection) I didn't know that was possible. 5% of jak2s got there in the blood »
CMR stands for Complete Molecular Response. Unlike PMR ( Partial Molecular Response), CMR means the mutated JAK2 is indeed not detectable. A DMR (Deep Molecular Response) is more difficult to define. Does it mean an AB <10%, or <2 % ? I suppose every research centre has its own definition.
I somehow thought CMR allowed up to 1% in some definitions, but I cant find any report I got that from. Undetectable makes the most sense for anything that is "complete". Could it be that what was undetectable used to be closer to 1%? I think early allele tests were less sensitive.
Another term "molecular remission" I think adds more gray areas to the options, maybe it's equivalent to "deep".
The report you link has a good clear set of definitions that are easy to understand. But as you say there seems to be no single definition or terms for all studies.
Molecular responses were defined as follows:
Complete response: 100% decrease in mutant cells
Partial response: > 50% decrease in mutant cells
Minor response: 20–50% decrease in mutant cells
No response: < 20% decrease in mutant cells
Anyone on hydroxyurea for calr positive? Any side effects?
Interferon side effects
Coping with itchiness and side effects of peg-interferon
Interferon negative side effects personal research
