I'm Jak2+ with P-Vera and 10+ yrs on Jakafi - basically since it was first approved for PV.
My recent labs and BMB results no longer fit neatly with PV and would be consistent with transition to MF: hypocellular marrow, anemia, WBC production abnormalities, increased platelets counts (450-550 from consistently in 200s), increased constitutional symptoms. However, my BMB shows no signs of fibrosis, and my doctor hypothesizes most of this may be due to my long-term Jakafi usage (hypocellular marrow excluded). While I wait for additional test results (MDS FISH, NGS myeloid mutation panel, viral tests) thought I'd check in here with others.
Has anyone been on Jakafi as long, or nearly as long, and seen a difference in bone marrow morphology and cellularity?
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interesting. You were put on jakafi but not the interferons or other options 10 years ago? I didn’t think insurance would cover that either, even though some of the data shows it make have some effectiveness-
Blood counts were not controlled on Hydroxyurea and I had severe splenomegaly (+ portal, hepatic, splenic vein thrombosis), causing a lot of pain, hence the decision to move to Jakafi vs an interferon. It has reduced spleen size by more than 5 cm.
I’ve been on Rux more than 7 years for PV, BMB last summer showed everything better than pre Rux 7 years ago. AB is allegedly 1.08%. It may be worth getting a second opinion from a MPN expert experienced with long term Rux.
I've had similar results; previous BMB was 3 years ago, after 7+ years on Jakafi/Rux, and AB was <1%. AB is now undetectable per last month's BMB 10+ yrs in, but I also have DNMT3A AB now at 5.3%. MPN experts near me are not experienced with long-term Rux for PV, b/c of the infrequency of use in PV patients (esp young patients) monitored over 10 yrs like me, despite being in the most populated state. Do you have a US-based recommendation?
I did not have DNMT3A prior to rux, and it has actually increased while on it. I've been taking 20 mg almost the entirety of my time on Rux. 2 BMBs prior to starting Rux in 2014 (1 immediately preceding) and only Jak2+ with an already low AB ~7%. BMB in 2021 had Jak2 AB ~1%, DNMT3A AB 4%. BMB Nov 2024 with undetectable Jak2, DNMT3A slightly increased to 5.3% as mentioned.
I'm in California and am seen at two of the top 10 cancer hospitals in the US and neither (UCSF, City of Hope) have PV (vs MF) patients who have been taking Rux for nearly as long as I have. I'm an edge case for a variety of reasons; young age at DX + severity of disease & symptoms + lack of response to 1st line meds makes it hard to find comparable folks as a "pioneer" PV patient taking Rux. Dr's were to consult with other specialists at ASH last week, will find out if that was fruitful at next appt in a few weeks.
I am not familiar with DNMT 3A is it a driver mutation?. I suspect most experts would say the change in AB from 4 to 5 % is not significant, also results can change depending if it’s done from blood or marrow, and also if tested separately in isolation or part of a NGS, also one lab can give different results to another. I had Jak 2 tested as part of a NGS in Aug 23 at a respected UK NHS hospital , my Jak 2 was allegedly 14.3% down from 21% the previous year. In Oct last year I had a Jack 2 done in isolation also from blood at Mount Sinai and it showed 1.08 %, my expert said Jak 2 testing in isolation is more accurate than as part of a NGS, I speculate that may also apply when testing other mutations. Also they say testing from marrow tends to be more accurate than blood, hence quite a few variables to factor in.
I note you appear to have acquired the DNMT3A while on Rux. I asked my expert at Mount Sinai if Rux can cause patients to acquire other mutations , he said no.
I also asked Dr V at MDA the same question, he said that patients on any meds inc Peg and Rux can acquire mutations and can also lose mutations, ditto to those not on meds but as to whether the meds mentioned can cause us to acquire additional mutations he also said no.
Your note that these mutation changes may be independent from any treatment makes sense.
I posted a bunch of reports long ago on DNMT3A emergent while on IFN (not Rux). The sample below discussed is one. But the %'s were all over place, with only the idea that it can happen being consistent.
This report was not about its time of emergence however and these reports are not real recent. None discuss DNMT3A emergence while on Rux, with only this unrelated note "response to JAK2 inhibition is impaired with concurrent ASXL1 and EZH2 mutations" We know IFN shares that result.
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On marrow vs blood, and single mutation vs NGS maybe it's esp important as VAFs get sub 5% or so. My recent VAF test lists a detection limit of 1%, so maybe different methods are indicated with very low values as you say.
DNMT3A aside, the primary question re: Jakafi effects long term is regarding cellularity & morphology vs ABs as my recent BMB shows hypocellularity and mild anemia (along with CBCs), which are seen with MF & fibrosis but no fibrosis was found. No other clinical explanation for the trend over the years of hypercellularity to normocellular marrow 3 yrs ago (attributed to rux) to now hypocellularity. Any insights regarding this type of change for PV patients on Rux would be super helpful.
I will ask my MP Dr next visit, as noted he has multiple 10 year Rux pts he said are "doing well". What "well" means is a worthy detail. But it's not till March.
If you do get an MF Dx you might qualify for the phase 1 trials of the new oral meds, Type 2 Jak inhibitors.
I think what you are asking is best answered by a MPN expert who has plenty experience with Rux. I suppose the simple answer but not the whole answer is Rux (like the other cyto drugs) will do different things for different patients. For some it controls counts , symptoms and AB completely, for others they get some of the above but not all, I also note you said you had a tricky start on the MPN journey.
Your doc may bring back some useful info from ASH but if it were me (and it’s not me) I would if possible travel to see the best experts and if possible show them a BMB slide and your lab history, that doesn’t always suit everyone but it is usually doible. I live in UK but took my slides to Mount Sinai where they were analysed by their pathologist and an expert Haem there. Prior to that I used to see expert at MDA Houston.
Thanks...was hoping to find someone else had a similar experience on Rux but it is a long shot. Will have to consider more travel after exhausting closer, California options. 2/3 MPN experts here at the major hospitals retired in the last few years so it's been difficult.
Very interesting. Please keep us up to date about your test results and any changes to your treatment plan so we can all gain new insights about the long term outcomes of PV patients who have been on Jakafi/Rux for 10+ years vs those on interferon for 10+ years.
One lady with PV on MPNs R Us Facebook group named Jean has had a similar long term experience to yours with Jakafi; i.e. her jak2 allele burden was reduced to undetectable, but some lingering mild symptoms remain. I believe she is still taking a modest dose.
my husband has also been on Rux for about 10 years ( previously intolerant to interferon and hydrox) and has recently been told after BMB that he has MF now. Doubled most recent dosage of Rux to 20 mg twice a day and seeing consultant at end of January.
Thank you so much for sharing. Do you mind also sharing what prompted the most recent BMB - changes in bloodwork, symptoms, etc - and your husband's age? Very rare to find another PV Dx on Rux for so long (though I've been taking 20 mg from nearly the outset). I may have another BMB done in Jan as signs point to MF and have been told fibrosis can be "patchy" and this most recent sample happened to have come from a patch without fibrosis.
my husband is 68, he was on 20mg for years and then reduced but now upping again since recent diagnosis. His white blood cell count had been going up and up over recent months. He has had bone pain in legs and pain under left ribs. But these have not been considered anything from haematology until recent bmb.
He was due another telephone appointment which is all he’s had since Covid but we have asked for face to face on next appointment.
My Dr has been involved with Rux since it was in trials. I asked him last visit whether he had PV pts 10 years in Rux. He does have some unspecified number of pts so. He said all are doing well.
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Jakafi side effects
Good news on mutant allele reduction on Jakafi.
Jakafi + Grapefruit
