Hi, I have PV Jak2+ (with high platelets) . I’ve been on ruxolitinib for the past year and half. I’m now on 25mg twice a day and still had no response particularly to my platelets and my platelets have got higher and higher as the year has gone on (higher than they have ever been ) . Has anyone else not had a response to ruxolitinib and if so, does anyone know the reasons people don’t achieve a response on it (particularly to platelets)?
I had a bone marrow biopsy this week as they said they are concerned about having no response to the ruxolitinib, so will wait for results of that. Thanks
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MPNpatient123
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I forgot to add I was diagnosed at the age of 18 - I’m 33 now (so had my MPN for about 15 years ) . I was initially diagnosed with ET but later around 5 years after I was diagnosed progressed to PV
I know that Pegasys/Besremi are affected by high levels of inflammation, reducing their efficacy but I don’t know whether Ruxo similarly impacted.
In particular smoking and additional mutations can disrupt the pathways used by interferons and I assume the same applies to general inflammation which can be reduced with an anti inflammatory diet and exercise.
Do you know your CRP levels (a measure of inflammation) and whether you have any additional mutations?
Hi, Thanks for your reply - I’ve never smoked, don’t drink alcohol and already eat an anti inflammatory diet and really into fitness/exercise etc to try keep as healthy as possible, so avoid any flammatory foods and eat a clean diet. I also do fasting.
My crp levels were checked last month and it was 2, so well within normal range.
They done loads tests to see anything else that’s causing it including vitamin deficiencies etc but all was okay .
The only thing that’s increased is my LDH and platelets.
They are looking for other mutations in my bone marrow biopsy they done on Monday to see if I’ve got any others, other than just the jak2 + but also to see if I’ve progressed to MF as they did say this would be the reason for the lack of response.
I’m hoping this treatment just hasn’t worked for some other reason rather than having progressed, so hoping for some answers /other explanations before my bone marrow comes back for some hope it’s not progressed.
I initially started my treatment journey on peg interferon but had no response to that either . Then was put on hydroxycarbamide for 3 years and again eventually lost response even on a very high daily dose still required regular venesections, so that’s why they switched me to ruxolitinib. I had high hopes for ruxolitinib but it just hasn’t worked for me sadly. Think I’ve just been unlucky with my responses to medication it seems compared to others.
Hello mpn123, I’m in the same boat as you! I’m having same issues where nothing lowers my platelets either, I’ve tried it all , hydrox, peg, Besremi , and now on Jakafi and still same . I mean they lower a little but I’ve never been in the range and I also started with ET 13 years ago and turned to PV after two years. I will be 55 in June. Doctors can’t understand why- even the mpn specialist that I no longer see . I’m a very faithful person and have all my faith in God whom I trust will never fail me. Currently my plts are in the 800’s on Jakafi .
Hi thanks for your reply ! Yes this was the same as me I was intially diagnosed with ET but 5 years later it progressed to PV and still have high platelets .
Have you had a bone marrow biopsy ? If so Did it show any other mutations or fibrosis ?
We know that we all respond differently to the medications used to treat MPNs. One of the reasons has to do with your individual genetic profile. Do you know which driver mutations you have and what the variant allele frequency is? Have you checked for the additional non-driver mutations? These are relevant factors. I would definitely ask for a complete genetic assessment.
Another factor to consider is co-occurring medical conditions. There are various conditions that can cause thrombocytosis. When one already has a MPN, these conditions can further increase thrombocytosis.
Hopefully, you will get clarification from the BMB results.
Hi I have JAK 2 postive , they told me when they last checked via the blood test when I was diagnosed 12 years ago it was at 17% . That’s the only test record they have of doing it so presume it has increased over the years .
They will be checking for other mutations and doing full gene profiling from the BMB sample they took I believe I will get results in 4-6 weeks they said for it all to come back.
I was initially diagnosed with ET but it later progressed to PV and i started requiring venesections along side them trying to control my high platelet count. I have always had high platelets because of that which have got under control at times with treatment but for some reason ruxolitinib has been ineffective for platelets and they have gradually increased more and more over the past year, now highest they have been. The ruxolitinib has however controlled my red count and they mentioned that’s going down so I haven’t needed a venesection on it which has been a postive. They have talked about trying a similar drug to ruxolitinib called Momelotinib or reintroduction of hydroxycarbamide along side it as I am on highest dose of ruxolitinib now and have been for some time, so no room to increase . Thanks for your reply
You might qualify for "compassionate use" of the investigational medicine Bomedemstat, or maybe enter a trial if that is an option. Compassionate use/expanded access is a USA term for access when there are no other practical alternatives for a serious condition and the pt does not qualify for a trial. It's up to the trial sponsor and has gov't procedures. You can inquire whether this type of access is available in UK, Bom is particularly for reducing platelets although it has broader benefits for MPNs. This is one of the various trials for it covering ET and PV:
Thanks for your reply . i unfortunately can’t take peg interferon . I was on that as my first treatment and i had no response to it - they kept trying and I developed a severe reaction to it where I developed high pressure in my brain so they had to stop it and not allowed back on it. I have been referred to an MPN specialist so will hopefully get some sort of answers then as my team are unsure what other treatments are available for me at the moment. Thanks
It doesn’t sound as if it’s progression. You mentioned Hydroxy worked but lost effectiveness, I know some veterans who say a drug can lose effectiveness after some years but can regain effectiveness after a period of years off it so retrying Hydroxy or possibly a combo of Rux and hydroxy may be an option.
I think getting all the results from BMB and mutations and seeing a few MPN experts would be what I would do and what I would recommend.
It will be interesting to hear what plan you end up with.
Hi yes I had no response to peg interferon and they kept trying to get a response over a period of a year but I went on and developed a severe rare reaction of intracranial pressure in my brain from it they think , so they stopped it and I am not allowed to go back on it . I was then put on hydroxy and after a few years of being on a very high dose and regular venesections my bloods were still not adequately controlled and I felt very unwell and developed numerous infections that I required hospital admissions for, so they then switched me to ruxolitinib.
Frustrating. Everyone responds so differently to these medications. I assume Besremi given that it's similar to Peg you would also avoid? You mentioned you tried peg in the past—was it the older PEG-Intron or the newer ropeginterferon alfa-2b (Besremi)? The latter tends to be better tolerated and more effective in some studies.
I only suggest it b/c the platelets tend to respond on these drugs. Here are a few things to discuss with your team.
Another JAK2 inhibitor, fedratinib (Inrebic), sometimes used in myelofibrosis or advanced PV/MF settings. Less studied in PV specifically, but may be considered off-label or via trial.
Clinical trials - hepcidin mimetics, BET inhibitors, telomerase inhibitors?
Statins might help in other ways. They aren't a direct cytoreductive agent, they wouldn't lower platelet production directly. But they might improve platelet function and reduce inflammation. The newer research on statins is interesting and they are well tested and tolerated in society.
You have been on quite a journey! MPNs are so different for everyone. I, too, am PV, JAK2 positive, diagnosed 5 yrs ago at age 69. I am on RUX 10 mg 2x daily. I have been in clinical remission for 38 months. One issue I have is the addition of the CLL clone, currently dormant. That clone was found as a result of rising LDH numbers.
One important question I always am asked by my hemo doctor is am I taking any new drugs, supplements or had any physical changes. A cardiologist wanted me to take blood pressure medicine even though my pressure is consistently in the 130’s over mid 70’s. When I asked if it was compatible with RUX, the answer was “How should I know? Google it and find out.” To say the least, I don’t see that cardiologist anymore.
Any drugs prescribed by any doctor should be verified as compatible with your treatment. For me, grapefruit in any form is a giant NO for RUX. Grapefruit, even in small amounts, it can negate the positive effects of many drugs.
None of this may apply but it is essential to look at this issue.
Best of luck - this journey can be stressful but you can handle this!
I have post ET myelofibrosis and I've been on Rux for 2.5 years. Rux has had no impact on my platelet levels at all.I currently take 25mg twice a day and hydrea and my platelets are still around 850. Without the hydrea my platelets would be over 2000.
The lack of response to rux is one of the reasons I'm having a transplant.
Hi thanks for your reply and Sorry to hear that you progressed to MF and I really wish you all the best for the transplant! . When you progressed how did they know was it showing on your bloods or through the BMB?
They think the sudden increase in my platelets to higher levels and increase in my LDH and lack of response to rux are possible signs I’ve progressed but I’m hoping not. I developed drenching night sweats as well around 8 months ago when my platelets started to rise and a lot of other symptoms like extreme fatigue again etc but I thought that was because my platelets weren’t being controlled.
Rux did control my bloods and platelets initially for the first 6 months when I started on it at a Lower dose, but after that my platelets just gradually started increasing more and more and they put my dose up but they couldn’t get them under control and still not even on the 25mg twice a day.
When I was diagnosed with MF I had stopped responding to interferon and my platelets were around 800. I also had an increase in LDH.
As I was only 42 at the time they didn't think I had progressed. A scan of my spleen showed it had grown mildly.
Initially they weren't going to give me a bone marrow biopsy, but as my fatigue continued to get worse, I lost 10kg, had drenched night sweats and some bone pain so they eventually did one.
The biopsy found that I had gained another non driver mutation and had fibrosis.
When my platelets were high n blood had thickened they used to take 400/600 ml of blood, I was taking aspirin then 75mg did that for 6 maths the started on trial jax2 n glopadodral been steady since, r u questioning Yr doctor, I give them the 3rd degree, used to write a note with all my questions, n would not let them go intill I was happy
Yes I am under the top MPN specialist in the UK I will be seeing her again when I get the bone marrow biopsy results come through.
I haven’t actually required a venesection for about a year and half now.
I am also on apixaban and clopidogrel alongside the treatment as I had a number of clots including eye strokes previously so I am monitored every 4-6 weeks and have been for the past 2 years so I am well looked after . Thank you for your reply
thanks everyone for your replies and help , I’ll update this post when I get my BMB results and also what the MPN specialist says when she sees me again on 29th to share why this hasn’t worked for me.
Just to add a note of hope. I went onto Peggy 14 mo ths ago and apparently from dropping my Neutrophils to 0.5 it had no benefit. That result in my injecting every 4 weeks at 45mg. I've now been 22 weeks without needing a venosection. I do spend 2 weeks of the 4 being very cautious about catching an infection but I'm actually happy with this.
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