I've been on Jakafi for about two months now, and I'm afraid that it doesn't seem to be working out for me. For the first six weeks, everything looked good: WBC and PLT in normal range and stable, RBC, HCT and HGB steadily declining but still only slightly less than normal. Because of the decline, my doctor decided to lower the dosage from the initial 140 mg/wk (10 mg twice a day) to 100 mg/wk (10 mg twice MWF, once a day on other days). However, RBC, HGB, and HCT continued to decline; yesterday's numbers were 3.65, 10.0, 30.2, while WBC (15.43) and PLT (569) were sharply increased from the corresponding numbers before the dosage change. Needless to say, this is very disturbing: apparent anemia along with high WBC and PLT. My doctor ordered all sorts of tests related to anemia (reticulocyte counts, lactate dehydrogenase, B-12, ferritin, iron); these numbers also suggested something is wrong. The bottom line is that I now have to come off Jakafi. It's apparently dangerous to do so quickly, so I'm now taking 70 mg/wk (10 mg/day).. Does anyone know the appropriate withdrawal protocol for Jakafi? Needless to say, I'm not feeling very well right now, most likely due to the anemia. Any suggestions would be appreciated.
Stephen
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Sorry to hear that the Jakafi is not working for you. Fortunately there are other options. Fedratenib and Pacritinib ae also options. More promising is Momelotinib (in clinical trials) which is indicated specifically for MF with anemia.
This is the only study I have seen on Jakafi dose reduction. There is likely more if you care to do a bit of research. mpn-hub.com/medical-informa...
I would be sure to take your question about the Jakafi dose reduction protocol to your MPN Specialist for a clear answer. It sounds like you will need to switch to something else. I expect it will be a relief to have a clear plan in place moving forward.
interesting paper you posted , I must say I am a bit sceptical where it says 92% discontinued Rux due to problems, for most Rux is easily tolerated for almost everyone , seems odd
Hard to say, but it does seem to be a quote of the study data. We would have to look up the original studies to be sure. Perhaps an issue when they were still working out the dosing??
The 92% was after about 4 years, so it is consistent. Mostly it was both of lack of response and toxicity.
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In a recent report discon rates are still high both in the later trials and real world use, this report includes Dr Harrison as an author, but 75% after 5 years is better than 92% after 4 from the early trial:
"In the phase III COMFORT-I [24] and COMFORT-II [23] clinical trials, approximately one half of patients discontinued ruxolitinib within 3 years and three fourths did so by 5 years [25, 26]. In clinical practice, ruxolitinib discontinuation rates can range from ~ 40 to 70% during the first year of treatment but are highly variable"
These rates are a surprise but it shows in more than one report so seems something to it. In other reports, anemia is a top reason for Rux discon, and the new momelotinib in trials is promising as an improvement here.
good info, the first paper is from 2011 and some of the results of patients reported are from 2007, that was early in Rux times, I seemed to think maybe it was FDA approved around then. In this paper most of the patients started on the max dose ie 25BID , this was the standard policy for MF until fairly recently by DR V and others , they have now changed that to start lower and build up to try to minimise anaemia and low platelets.
The second paper from 2020 paints a better if not ideal, I suppose what makes the figures look poorish ( and I haven’t read it in it’s entirety) is the unfortunate fact that Rux for MF for many loses effectiveness around 3.5 years, some are still good 10 years plus on it. Dr V has one he talks about who is on it since 2008 and as far as I know still on it.
Certainly the figures for the first 3.5 years here seem poorer than what I hear about at conferences and on line for MF.
It’s probably important to point out response/ failure rates in these papers here are for MF , response rates for PV are very different. When I asked DrV in 2018 what was the time period for Rux losing effectiveness with PV he said he at that time hadn’t seen any lose effectiveness, I have heard any anecdotal reports either.
You're right about the info being directed to MF. Dr Harrison's comment would be in that context. It makes sense that Rux can have better numbers for PV. Is Dr V avail to you to ask for his latest experience on Rux for PV?
he will be available if I pay :-). I think if there was a problem with durability of Rux for PV it would be on the forums or mentioned at the recent conferences. If I hear anything to the contrary I will of course post.
Sounds expensive and best saved for the most important needs.
IFN has some question too on longevity as I've posted, at 6+ years it seems some can lose molecular response. But we do see shorter times than that in some contexts for Rux. Any info you can find is helpful.
The withdrawal rate does seem quite high, which in itself is concerning. I'm still waiting to hear back from my UPenn specialist group about scheduling a tele-visit (originally supposed to be today but unaccountably canceled). All of these new medications, including momelotinib, are being tested/approved for MF; I suppose they could be used off-label for PV, but I would like to see some specific results before trying such a new medication.
Thanks for your feedback. Unfortunately, neither fedratinib nor pacritinib are on my formulary. I will try to speak with my MPN specialist as soon as possible, and also put her in touch with my local hematologist.
There are often ways to get a medication approved when it is not on your formulary. This includes Medicare Part D plans, which I am also on. I had to work through the process to get two non-formulary medications approved, including Besremi. I wrote my own appeals in both of these cases, and succeeded.
It is unrealistic to always expect providers to file the appeals for us. Each plan has different rules - "Plan Rules" - that drive how a medication is approved. Mounting a successful appeal is based on understanding how your Plan Rules work. Sometimes, preemptive research can guide how the original request is made, but not always. It took me 14 hours of phone calls and additional research on-line to put the appeal for Besremi in place. There is no way my provider could have done this for me. Sometimes we have to be our own best advocates.
If you do not have the time, inclination or skill set to do this, in the USA you can contact a Patient Advocate who can help. Here are some links to that in case you are interested.
Thanks for this very interesting information. I'm on a Medicare Advantage plan with their own formulary. My insurer is a spin-off of a highly regarded Kaiser-style medical system that has been working in (mostly rural) North-Central PA for about a century. I'm not sure that makes any difference to how they would react to an appeal.
The specific plan you are on does make a difference. Each plan has its own plan rules and formulary. There will often be a way to get a non-formulary medication approved.; however, you have to know how the plan rules work.
Some plans post the rules on their website, but not all. You may need to make phone calls/emails to obtain a copy of the plan rules. Once you have these, the process for appealing a denial successfully is more clear.
When my plan denied the Besremi, I called in to request a copy of the plan rules that were cited in the denial. The "Patient Navigators" were unable to find the plan rules and provide them to me. I ended up filing a Medicare Grievance due to the denial and inability to provide a copy of the rules. In the process, it turned out they had not followed proper procedure in processing the denial in the first place. By the time I had my doctor refile, they told him not to bother because they had already approved the Besremi due to the grievance I filed. Persistence sometimes overcomes resistance.
I hope you will be able to pursue another option even if it is not on your formulary. Perhaps you can also talk to your MPN Specialist about participation in one of the clinical trials, like Momelotinib.
Thanks for the input and guidance. I spoke with my UPenn specialist this morning; she told me that anemia is a known side effect of Jakafi, and that the goal is to find a dosage that keeps anemia within limits while also keeping platelets under control. I will try this for a while and see how it goes. She also said (with a smile) that she couldn't answer my question about splitting pills. I took this as a clear indication that splitting pills is OK.
Maybe [likely] I missed something, but why aren't you on or considering and interferon-based treatment?
Based on my research after my diagnosis earlier this year, they seem to be the most promising therapies with an eye toward improving longevity, quality of live, and even disease-modifying effects.
Thanks for this suggestion. Based on what I've been reading on this site, I'm also looking at interferon. That being said, when my UPenn specialist recommended that I go on Jakafi, I saw no reason to doubt her recommendation. I will be having a tele-visit with her tomorrow and will definitely mention the interferons. Pegasys is on my insurance plan's 2022 formulary and Besremi is approved for 2023.
I was offered Jakafi, and turned it down in favor of Besremi, and honestly, if the Besremi doesn't work out, I'm going to try Pegasys instead of falling back to Jakafi- I like the possibility of molecular remission that IFN-based treatments offer, and don't like the side-effect profile [and failure rate] of Jakafi.
I wasn't aware of the failure and withdrawal rates reported for Jakafi until recently. That being said, the reports I have seen refer to patients with MF. Are there similar reports for Jakafi recipients with PV? How is Besremi going for you?
My doctor said that anemia is a known side effect of Jakafi, and that the goal is to find a dosage that keeps the anemia within limits and platelets within bounds. I will have a CBC on Friday and will then see how the dosage can be adjusted. She didn't mention the interferons and how they fit into the picture. What are the downsides of tinkering with the immune system?
Has your Dr given specific reason for the Rux preference? Hope you can get more info tomorrow.
My Dr (MPN specialist) recommended Rux to me. I'm PV with ET flavor. He was involved in some of the early Rux studies. He said it would be the best for improving symptoms (very tempting) while IFN could be less so. But he also said Besremi is good medicine, this was just after Bes approval.
I went with the IFN for its consistently better allele burden (AB) reductions, hoping to have that benefit even if I might suffer more on it. I stressed over this choice for a while. My symptom burden is not improved so far on Bes vs HU, but they are different. But my Jak2 AB has decreased at 6 months. (14-10%) I look fwd to next year where dosing should go to 1/month.
As ainslie here notes, Rux is PV approved but does not have the depth of info that MF has on Rux.
No, my doctor gave me no reasons for preferring Rux over the interferons. She also said that anemia is a known side effect of Rux, and that the goal should be to adjust the dose to keep anemia tolerable and platelets within limits. When I asked her whether the pills could be cut, she replied that she preferred not to answer. The implication was clearly that this was a reasonable (and cost-effective!) approach. I'll go ahead and start experimenting with dosage.
Has your Dr discussed a marrow biopsy? It's likely this could provide more info on the something wrong if the tests planned don't provide clear answers.
Sorry to hear it's not agreeing with you.I was the same....had to come off and it was quite a slow process of withdrawal.My doctor put me on lenalidamide(revlamid) I am cross MF/MDS and it was great for me for 2and half years....no transfusios now transfusion dependent as medication stopped working and I had other complications i.e lots of flare ups of my Bronchiectasis and now on hydroxicarbimide to reduce high platelets. It's a juggling act for me trying to cope with both conditions as well as inflammatory arthritis which is another which has cropped up recently. I realize MF is part of the reason I am getting so much inflammation.Thank you for listening!! Don't worry your haematology doctor should put you on the best medication.
Lynn, sorry to hear that you've been having so much trouble. I was diagnosed with PV back in 2015, but perhaps this diagnosis will need updating. My job for the coming week will be to coordinate my local hematologist with the MPN specialist in Philadelphia.
I would be inclined to do the tapering down with guidance from your doc or Haem nurse, only they know your exact medical position, taper is important though
My husband is on jakafi been on it three years now.
He took ill on holiday in Mexico with a severe episode of vertigo .
My sister rang his consultant he said just stop the jakafi for the 10 days we had left on our holiday and restart it when you come home . He said it won't do you no harm.
So my husband followed his instructions stopped suddenly as he couldn't stop being sick.
Anyhow he restarted the jakafi when we got home his bloods remained the same he had no change he's had repeat bloods done within 4 weeks and all fine.
I was worried about my husband stopping his medication but in all he was ok x
I read that Jakafi withdrawal syndrome seems to take a few weeks to set in, so 10 days off might not be so risky. i'm glad to hear that it all turned out well for your husband. I know what severe vertigo can do - I had a terrible experience with severe vertigo. In a few minutes, I went from normal to being unable to stand or sit. This turned out to be an inner ear infection that cleared up in a week or so.
That was certainly the case when I had suspected 'sudden withdrawal syndrome'. I can't now remember exactly but it was at least 3 to 4 weeks after my dosage was dropped too quickly that I got ill.
My husband was diagnosed last Friday with BPPV so in all its not serious but it's had terrible impact on my husband's day to day life. We paid for him to see a physio to do the eperley manovure on Friday so far it's not worked, but it can take upto a week. He's on bethistimine for two weeks. So after he's finished these tablets on Friday if he's no better he has to be referred to ENT which will be about a 6mth waiting list 🤷🤷.
"When discontinuing Jakafi therapy for reasons other than thrombocytopenia, gradual tapering of the dose of Jakafi may be considered, for example by 5 mg twice daily each week.
Thanks for sharing this. I also have this insert, but I put it aside since the font was far too small for me to read easily without magnification. In hindsight it would have made sense to download it so that I could easily see it on the screen.
You're completely welcome- I know what you mean, at times I have had to use my cell phone's camera to magnify small print to a more readable font size.
As I noted before, I didn't see anything about Interferon in your posts- os there a reason you're not a candidate for it, or why it's not an option for you?
You're right about the Dr opinions. IFN has been used for MPN since at least the 80's, the Silver MPN group at Cornell is a pioneer of it. But the early IFNs were quite harsh since they led to large up/down levels in the body and many adverse reactions. So many Drs considered (and still) IFN to be toxic. I actually remember the fuss and then disappointment about IFN in the early 90's before I had a reason to care.
The IFNs we use now, PEG and Besremi, are pegylated. Pegylation is like a time release pill that slows down the release of the med to keep a constant IFN level in our body. So there is enough IFN to do the job but it doesn't peak so high in us as to kick our b*tt.
Another problem is even with pegylation PEG was originally for hepatitis, and doses were huge, 180mcg was common as a starting dose. This is way more than most MPNs require, esp to start, but Drs used that dose anyway. Even with pegylation that much can cause adverse events for many and thus the continued bad reputation.
With the recent approval of Besremi for MPN IFN is now official. But with that history above many Drs are influenced by the past and are wary.
-For us we know IFN is a viable and potentially best option when dosed right and it should absolutely be part of discussion with Dr. But still not all can tolerate even the most careful doses, same as all our other meds.
I think that may be it- I had done a lot of reading already between my presumptive diagnosis by my PCP/Family Med. MD and getting in to be seen by my local general Heme/Onc MD, where the diagnosis was confirmed, and thus had pretty much settled on INF as my tx of choice.- but as I previously related elsewhere on here, she wasn't very familiar with modern INF choices, or their use in treating MPN's.
For that reason, she started me on HU, while I looked for an MPN specialist Heme/Onc MD, and found Dr. Wang at Roswell Park. They agreed that Dr. Wang would initiate my tx and stabilize my dosage [as much as possible] and then I would revert back to my original MD's care.
Apparently the general Heme/Onc's are used to the original interferon formulations and using them at really high doses to treat Leukemia's- and they are gun-shy about the use of more modern formulations [Pegasys and Besremi] which have less side-effects and typically work in lower doses for MPN's.
At the even the specialist offered Jakafi and then accepted my firm request for IFN as a 2nd choice. But again, I'm by all counts a 'young-old man'- no othr systemic diseases and no history of clots.
I'm sticking with Jakafi, at least through my Friday blood work. I'm not really happy with the fatigue and weakness associated with the anemia, but I'm ready to give it a bit more time.
Thanks for the additional history. I find the division of opinion in the MPN medical community a bit strange, but if I can't deal with the anemia or if it gets worse, I'll be more aggressive in going down the interferon path.
We're in a transitional period in MPNs, IFN is getting its day in the sun, but not all Drs see the light hence the mixed advice.
After many years, we're better learning the benefits and limits of Rux. Likely IFN will have the same learning process and the divisions may get better.
There seem to be two therapeutic sects: one prescribing JAK inhibitors, and the other prescribing interferons. What is needed is are some research studies directly comparing the two approaches and trying to identify diagnostic features that make a patient suitable for one or the other. However, this may take some time, and I'm already 78
There is actually just such a trial right now that should finally give a real comparison. But you're right it's not ending till later this decade. Part of our familiar routine, our disease takes a long time to get answers.
Thanks for sharing the link to this trial, which should answer lots of questions about the two MPN therapeutic approaches. However, it's most likely of little direct relevance to me, since by the time the study is finished I will be approaching my 85th birthday
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