Fostamatinib, low dose prednisone, and high dose nplate triple therapy?

It failed the Rheumatoid arthritis trails and the IgA Nephropathy trails are not proving too successful either. It is hasn't been licensed in Europe for ITP treatment as far as I am aware. Certainly hasn't in the UK.

Hello All,
I am having my worst week ever since being diagnosed with ITP in May of 2017. I went back to hemo yesterday after my Friday IVIG appointment and my platelet count remained at 3k. Unbelievable. Furthermore, my vitamin D level was 20 (normal is 30 to 100). I am taking 3000 units per day of vitamin d to elevate my count. I told doctor that I am dumping the 20mg of prednisone for the next 4 days as I will be taking a dexamethasone pulse. I am bruised all over my body....literally..with a big bad one just behind my elbow. Doctor gave me a level 10 Nplate right off the bat. I am going back to my hemo tomorrow for another IVIG, plus I can't shake this bronchitis. My birthday is Saturday and my bachelor party is from Thursday to Sunday in Nashville. I guess God said no fun for me for now. I honestly don't care. I just need to get something...anything to jack up these counts to at least 30k. This is not good.

So just for the record...as of this moment..I am on a Dex Pulse that I started last night and will end on Thursday. I am on level 10 Nplate as well. I had IVIG on Friday and it is now Tuesday morning with no upward movement in counts. I have another IVIG that I will be doing tomorrow. Finally, doctor removed me off of the Fostamatinib last week.

Hal.....this last paragraph is for you. Remember when I had my sunburn and my levels went to 158k back in mid June. Well, since I have low vitamin d.....do you think the sun (high in vitamin d) could have put my vitamin d levels into hyper drive...briefly....and help briefly correct my ITP until my sunburn went away (aka...my vitamin levels went back down to its normal level of 20) ...since I avoided the sun for healing purposes. I know it sounds ridiculous but could there be a correlation? I know that I can't heal my ITP by getting sun burnt all the time but I just wanted to know if you could see a correlation..that's all.

I will keep everyone updated. I just hope I bottomed out now and there would be better results ahead. I am just trying to make it to September 10th, when I am in London for my Indium scan.

Jason

I think you are wise to stop Pred whilst on Dex but you will need to start it again afterwards otherwise you will be at risk of an adrenal crisis.
Steroids of course make one more susceptible to infections and more difficult to fight them hence the inability to shake off the bronchitis, which in itself may well be responsible for the low platelet count. My count always crashes if I have the merest hint of an infection.
Regarding vitamin D I have been on supplements ever since my steroid induced osteoporosis was diagnosed. My levels run slightly higher than normal levels and have had absolutely no effect on my count at all.

Hi - I'm new here and reading around...My three year old son was diagnosed July 6 (2018). Thanks for sharing your story. I'm sorry to hear about your birthday and bachelor party. I hope you can take it easy with the bronchitis. Are they treating it with antibiotics?

Jason:

Low Vitamin D seems to be an epidemic, especially in those with autoimmune disorders. I have chronic low D and have to take high doses all the time....have for years. 3,000 IU's per day is a low dose. It's pretty normal to be prescribed 50,000 to 100,000 IU's per week to get low levels up.

There have been studies that show that low D can contribute to autoimmune disorders. That doesn't mean that getting D levels back to normal will cure the disorder. I doubt that the burst of D that you got from the sunburn was the reason that your counts went up. When a person has a sunburn, white cells rush to the skin to heal the damage. Simply put, platelet destruction was slowed because the white cells were distracted. It's possible although I wouldn't put any money on it.

Hopefully your counts go up some so that you can enjoy your party!

Oh wow, a very difficult time. That sounds like a bit of rebound thrombocytopenia - like some get when abruptly stopping Promacta/Nplate. For some, the B cells seem to throttle up to red line to clear out the evil platelets. Mrsb, did you recall having extreme count crashing when discontinuing Fostamatinib?

Ah, that 158 back in June. I remember it well. Your could have it exactly right. One guess is as good as another. So many variables. Sandi could have it too. The only thing I'd add would be that there is a finite number of lymphocytes. They can only do so much at a time. Or, the immune system may have a destructive pecking order whereby things like skin burns have priority. I dunno.

About your doctor. You're on: a Dex pulse, Nplate 10, and regular IVIG now. But some how, that combination is safer (clot wise) than just Nplate dose X and Fostamatinib combination? I'm having trouble with that logic. I wonder if your doc got way outside his comfort zone with Fostamatinib. Or, do I have him wrong?

Hello Hal,

I got IVIG this past Friday when I had a count of 3k.
Hemo sees me again on Monday and my count is still 3k.
Hemo gives me a Level 10 Nplate shot and says to me...I want to see you on Wednesday. If count is not good..we are giving you another round of IVIG. Also..he said that we will be removing 20mg daily of prednisone for the next 4 days because you are going on a dex pulse. We need to get your count up now.

Please keep in mind that between June 15th and today...I only received 1 Level 10 Nplate shot (July 6th) after he deemed that fostamatinib at 100mg was not working. He immediately took me off of the Level 10 Nplate the following week because he said that Fostamatinib and Nplate dont play well together.

Now I am completely off of Fostamatinib (100 and 150mg), which means I am free to return to Nplate. If my count is good on Nplate then tomorrow's IVIG is off the table, but I highly doubt that.

Really interested in this Etanercept (Embril) and its impact on T Regulatory Cells with persistent continuation of ITP. I like to blaze serious paths toward a cure. I do not care if I am the guinea pig. This is science and it can be figured out.

By the way. Sandi is right, "the higher the white count, the better the platelet count". I do see a correlation here. My white count is higher when on an immunosuppant and my platelet count is a bit better. When my white count is in the normal range, my platelet count dips to low levels.

My London schedule is as follows: Indium scan on September 10, 11, and 12 at St. Barts Hospital followed by a 4:00pm consult on September 12th with Dr. Drew Provan at Royal London Hospital followed by flight home to NYC.

Thanks all for your support and I will always keep you updated. I did tell Dr. Provan I was part of the Platelet Support Association.

jasondema wrote: Really interested in this Etanercept (Embril) and its impact on T Regulatory Cells with persistent continuation of ITP. I like to blaze serious paths toward a cure. I do not care if I am the guinea pig. This is science and it can be figured out.

Jason, you'll care if all of these drugs end up damaging your health. It happened to me. I ended up with long-term ITP remission but my health has been severely compromised. I'd rather still be dealing with ITP. There is no hurry here, really. Remissions do happen and sometimes slowly managing ITP can get you there.

Another thought - I understand why your doctor stopped Fostamatinib, but I wouldn't consider it a failure. It wasn't give enough time. However, it does not seem to have a great track record so it's probably not a big loss.

Dr. Provan is the best there is! I thought he retired though? You're very lucky to be able to see him! He always has great advice. He did a great video in 2010 that you might want to watch. fhs.mcmaster.ca/medicine/hematology/ITP-2010/player.html

Hal wrote 'Mrsb, did you recall having extreme count crashing when discontinuing Fostamatinib?'
It never raised my counts so there was nowhere for them to drop to.

Sandi wrote 'you'll care if all of these drugs end up damaging your health. It happened to me. I ended up with long-term ITP remission but my health has been severely compromised. I'd rather still be dealing with ITP. '
I couldn't agree more. I now have to contend with steroid side effects of osteoporosis, raised intra ocular pressures and bilateral cataract formation.

jasondema wrote: Hello Hal,
...
Please keep in mind that between June 15th and today...I only received 1 Level 10 Nplate shot (July 6th) after he deemed that fostamatinib at 100mg was not working. He immediately took me off of the Level 10 Nplate the following week because he said that Fostamatinib and Nplate dont play well together.

Now I am completely off of Fostamatinib (100 and 150mg), which means I am free to return to Nplate...

Right. He was using steroids and IVIG as rescue. I wonder if he should have faded those and pivoted to Nplate as rescue.

To be honest, him saying Fostamatinib doesn't play well with Nplate doesn't mean anything to me. One could just as easily say steroids and Nplate don't play well together, because they don't - hence all the concern about clots. I would have pinned him down on what he meant or had heard.

My guess is this doctor is not that familiar with combination ITP treatments (combining immunosuppressants, eg Azathioprine and Cyclosporine). If it were me, I'd ask him about it. If he's not, I'd start looking for a doc that was, soon.

Also. Are you aware that the risks of a blood clot from ITP treatment is much higher if one is asplenic?

Hello All,
I just got my platelet count done today and it went up to 13k. Tomorrow is my last day of a 4 day dex pulse and then I go back to 20mg of prednisone daily on Friday. I will not be getting another NPlate shot until next Friday. I typically get an NPlate shot every Friday but I can't this week because I am traveling to Nashville, TN tomorrow through Sunday. I was given another round of IVIG today. I guess that I just have to hope that the NPlate kicks in soon.

Hal...I am not asplenic yet. I still have my spleen. I am going to London to see if it is my liver, spleen, or both. I am about to be 41 years old on Saturday. If it is my spleen, then the success of a splenectomy goes down as I age. I am at the fine line age wise of where a splenectomy could still prove to be successful. I am in a tough spot because nothing is working effectively from what I have tried. I have a consult with Dr. Provan at 4pm on September 12th. I hope he can provide me some guidance as well.

In my case, I have been spleenless since 2006 and have never had a blood clot. But then, every case is different.

jasondema wrote: ...
Hal...I am not asplenic yet. I still have my spleen. I am going to London to see if it is my liver, spleen, or both. I am about to be 41 years old on Saturday. If it is my spleen, then the success of a splenectomy goes down as I age. I am at the fine line age wise of where a splenectomy could still prove to be successful. I am in a tough spot because nothing is working effectively from what I have tried. I have a consult with Dr. Provan at 4pm on September 12th. I hope he can provide me some guidance as well.

Right. Just thinking ahead on my part. My guess is that the Indium scan is going to show strong spleen destruction, which will give credence to a splenectomy. I was just pointing out that if the splenectomy fails, all these platelet count rescues will have increased risk. Few folks need steroids, IVIG, and Nplate all at once to keep one's head above the water.

Meeting with Dr Provan should prove well worth it. From the studies I've seen with his name on it, he has contributed more than anyone else in raising the standard of ITP care to what it is today. Ha, maybe I could play like a distant relative and go in with you to see him.

Sandi wrote: ...
Dr. Provan is the best there is! I thought he retired though? You're very lucky to be able to see him! He always has great advice. He did a great video in 2010 that you might want to watch. fhs.mcmaster.ca/medicine/hematology/ITP-2010/player.html

Sandi, I was watching this video by doctor Provan again. In particular I was noticing 'Slide 4' at the end of the segment, at time 1:50. When he talks about eventually having 'ITP types' I think the guy may be on to something. That different patients have different ITP issues going on.
What do you think?

Oh I believe that there are different types for sure, but no one (other than you) has really identified them yet. ITP has come a long way, but still has a ways to go. When I was diagnosed in 1998, they didn't know that people with ITP had production problems. It was all thought to be purely destruction. There was no known link between ITP and thrombotic issues. There were no TPO's.

I know that newly diagnosed get frustrated with the lack of knowledge about this, but having been in it for a while, I can see major strides in the last 20 years.

It is interesting that the good doctor enumerated two of the more unusual ITP issues in the video. Inadequate TPO (me?) and lysis of megakaryocytes (jason?). Both of these, in effect, lead to a shortage of platelets, and are not the commonly understood platelet destruction issue.

It's been 8 years since the video.
It's been almost 2 full years since this study claiming four types.
"Autoantibodies to Thrombopoietin and the Thrombopoietin Receptor in Patients with Immune Thrombocytopenia"
My ITP table is a year old this month.

I have to wonder if money / new drug patents is keeping this insight hush-hush to public purview for now.

I know that the presence of autoantibodies seem to dictate a 'type' of ITP, but I think it's even more complicated than that. I think there is much more going on that hasn't yet been discovered. Autoantibodies to thrombopoitetin sort of leaves a person SOL. Why does this happen? That's the question of the century.

Hello All,
A few things to update:
My last 2 Friday appointments yielded counts of 56k on August 10 and 38k on August 17. I am on level 10 NPLATE and 20mg of daily prednisone only. I have 2 Friday appointments left before I travel to London (St. Bart's) to do my Indium Scan on September 10-12 followed by a late afternoon September 12th appointment with Dr. Provan at Royal London hospital across town.

By the way...Hal and Sandi...check out this new ITP discovery...see the link..
www.sciencedaily.com/releases/2018/08/180814150943.htm

AND if you really want to get into deep medical terminology..check this out
www.pnas.org/content/early/2018/08/07/1807000115

This might help with the whole "thrombopoitetin sort of leaves a person SOL theory"

We just might have a new alternative.

Yes, that sounds promising! I wonder how far off that is? The article was very recent.

This is just what I was talking about. There is SO much more to discover!

Not sure my message posted. I went to england for the indium scan a few years ago and met with dr provan. He was wonderful. I did post where we stayed and details about what to expect. Maybe sandi can tag it for you or you can search uner my name to find it.
Emily

Ah, a 56 and a 38. Nice. Finally got stabilized again without IVIG.

Very interesting find Jason. I read the first link, but wowa, the second one, that is extreme. Towards the end they talked like they could get something going/developed to supplement the existing TPO mimetics (Nplate and Promacta). I wonder why supplemental. One would probably have to read the whole thing to figure out why something standalone isn't under consideration.

Jason, I think this is the thread EmilyK was wanting you to see about her Indium scan.
pdsa.org/discussion-group/7-treatment-general/28639-indium-platelet-scan-at-barts-hospital-london.html#47758

If I'm reading right, she was on 50mg of Pred for the test - and she responds [strike]strongly[/strike] ok to Pred.

Hello All,

Just an update, I went to London and did the Indium Scan from September 10th through the 12th. I should have results by this Friday or next at the latest. Furthermore, I got to have an hour consultation with Dr. Provan on September 12th prior to leaving the UK. I am back home in NYC. My last 2 platelet count readings on September 14th and September 21st were 91,000 and 83,000 respectively. This was while I was on Level 10 NPlate and 20mg of prednisone. I just tapered to 15mg of prednisone this weekend and I have 1 blood blister on inside of mouth. A little concerned but hopefully my counts are boosted up on 15mg of prednisone by the time my next visit to my hemo on Friday.

Regardless, I told Dr. Provan that the following: Dex pulse keeps me good for a week and then that is it. Prednisone by itself does not help much. Rituxin failed.
Fostamatinib failed. I still have my spleen. IVIG is good for at most 3 weeks then it stops working. Promacta at 50mg and 75mg yielded no results. NPlate by itself yielded low counts as well. Only successful thing is Prednisone in 10mg to 20mg range coupled with Level 10 Nplate keeps me ok but I can't stay on prednisone forever.

His response was to stay on my full-dose Nplate and adding in
mycophenolate 500 mg twice daily for one week and then have a review, a CBC and if all is good
(no side-effects; these are uncommon) increasing the dose to 1 g twice daily. I would
need to stay on mycophenolate 1 g twice daily for two months before deciding whether it has
worked or not. If it does work I would start to taper your steroid dose down over a few weeks with
a view to stopping the steroids completely. If, after two months, there is no response to this combination we could switch the Nplate to
Promacta. He suggested 75 mg of Promacta daily along with 1 g twice daily mycophenolate and
again give this two months to see if it has an effect. The other thing is
that Promacta can be increased up to 100 mg daily as many others do use it at this dosage.

IF all fails by this stage than a consideration for a splenectomy option if the indium scan
shows a pure splenic or predominant splenic pattern. If the scan does show one of these then the
chance of response to splenectomy is very high. This was Dr. Provan's response. I will keep everyone updated.

Thanks for the update!

Jason, good to see you posting again. Well, there it is. How to get treated with MMF. I get the impression that it acts more like a switch and that proportional dosing doesn't really work with it.

On the switch over to Promacta. Did he mention doing that because of the possibility of developing antibodies to Nplate? I came across a study recently that talked about leveraging Cyclosporine to correct antibodies which attacked an earlier version of Nplate.

Was there any problem getting the scan done while being on, I presume, Nplate and Pred?

That's a long wait for Indium results I got mine instantly. Not that I really needed to be told as I watched the whole thing.

Hello All,

I just got my results and I do not know whether to be disappointed or not. My platelets today are at 16k while on level 10 Nplate and 15 mg daily of prednisone. They are getting me ready to go on Cell Cept. My indium scan results are below.

Spleen to Liver Ratio
30 minutes = 3.05
2 hours = 3.21
24 hours = 3.63
48 hours = 3.09
Half clearance time = 0.83 days
Platelet mean life span =1.2 days
80% destroyed after 1.93 days
This corresponds to a spleen / liver ratio of 3.24

Impression: The results are compatible with a mixed liver / spleen platelets sequestration, significantly more prominent in the spleen than the liver.

I do not know if this means that it is mixed hepatic or does this mean that it is predominantly splenic based on the impression comment.
Can someone tell me what this means and is this a good report to go through or not with a splenectomy. It is not 50/50 equal damage between the spleen and the liver based on the doctor's comments but this is all that I am gathering so far......I would assume. Thanks.

When i met with dr provan he gave me his email address. If he did the same for you, ask him his thoughts. He was very anti surgery when I saw him but that was probably case specific.
Emily

When i met with dr provan he gave me his email address. If he did the same for you, ask him his thoughts. He was very anti surgery when I saw him but that was probably case specific.
Emily

Hi Jason: concerning your inquiry about your Indium scan, I went to St. Barts in 2013 and my results included a 6.17 spleen/liver ratio, to which they concluded "findings are compatible with a purely splenic platelets sequestration (Dr. Biassoni)." In looking at your results, it appears that your platelets are being destroyed at a much faster rate than mine (e.g. 80% destroyed after 1.93 days for you vs. 9.66 days for me) which leads me to believe there is more going on than just the spleen.
Nonetheless, despite my relatively strong Indium Scan results re:"Purely" splenic sequestration, in fact my 11/13/18 Splenectomy failed to make a difference, with my platelet count dropping from a high of 100K the day after surgery to 4K yesterday. The reason that I finally did the Splenectomy is that I had dropped to 7K on 75 mg of Promacta, with an average in the low teens for the past year--a pretty weak response. The other reason is that I would have always wondered whether the "whole thing" could be over with a Splenectomy, and so I took the gamble just to know that this would or would not fix me. On the positive side, the surgery was relatively easy--I had a laporoscopic procedure and was up and around in 2-3 days, with no problems, and so far, no infections (which was my greatest fear). While your Indium scan was not as strong on the Splenectomy as mine was, I would not rule it out, especially if you are young (I am 67 and the success rate diminishes with age). I hope this helps you with your decision making--as many of the folks have posted on this site, we all need to find the particular treatment that seems to work best for our individual situation--I truly wish you the best in finding that treatment for yourself.