Tavalisse, experience

Like to know if anyone here has had any experience with Tavalisse, and what if you don't have a spleen. In that Travalisse is a spleen (SKY) tyrosine kinase inhibitor.

A Clow, here is a report on Fostamatinib (aka Travalisse) phase 3 FDA trial.
www.raredr.com/news/phase-3-data-fostamatinib-published
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Fostamatinib produced clinically‐meaningful responses in ITP patients, including those who failed splenectomy, thrombopoietic agents, and/or rituximab.
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Sounds like you're good to go. Best of luck to you and Kimberly.

I also am interested in Tavalisse after having a failed Splenectomy 2 weeks ago. Did you ever take it, and if so, what has been your experience?

FYI: I did OK on Promacta for 5 years but my numbers kept dropping (into the low teens) even after I maxed out the dosage of 75mg, so I decided to do the Splenectomy. While I have no regrets (yet!) I felt like I would always wonder if I could be "cured" with the surgery, and at 67 years of age, I didn't think I should wait any longer...

Luca, have you ever tried a low dose Prednisone with Promacta?
Several folks that I have seen, who lose response, do well with that combination to get back to a lower Promacta dose.

Thanks for the suggestion Hal; I'll ask my Hematologist. No medical person has suggested that yet, and I suspect that there is reluctance to use Prednisone--even at a low dose--for prolonged periods of time due to its side effects. But, as I'm forced to look at all alternatives, I will certainly look into it!!
Meanwhile, it is interesting to note that I have not yet heard back from anyone who has tried or has been on Tavalisse...

I participated in the FIT trials both double blind and open label extension. It never did a thing for me I'm afraid. The other lady from my clinic who also participated had a moderate response for a year but after that was back down to counts in single figures. It hasn't been licensed in the UK or anywhere else in Europe.

luca wrote: Thanks for the suggestion Hal; I'll ask my Hematologist. No medical person has suggested that yet, and I suspect that there is reluctance to use Prednisone--even at a low dose--for prolonged periods of time due to its side effects. But, as I'm forced to look at all alternatives, I will certainly look into it!!
Meanwhile, it is interesting to note that I have not yet heard back from anyone who has tried or has been on Tavalisse...

Luca, I don't respond to steroids, at all, which may be the reason why I find myself suggesting them to others. It's not me that has to take them. On the other hand, I see them as a useful tool for ITP that isn't available to me.

As an example, 'Lman' recently levered Pred with Promacta combination. He started at 25mg and it took some 12 weeks for full response.
pdsa.org/discussion-group/7-treatment-general/30054-rituximab.html?start=30#65128
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... counts checked every two weeks ...
... 60 (25mg), 148 (20mg) , 47 (15mg) , 50 (10mg) , 90 (7.5mg) , 203 (5mg) ...
"
As you can see 20mg appeared to be very effective. Lower doses were more of a accumulation over time thing.

Are you taking 50mg or 75mg of Promacta now, for a modest improvement?

As for Tavalisse/Fostamatinib. The only person I've seen here with a reported good response is 'sachmo16'. Note that he/she responded to IVIG and was using regular IVIG treatments before then. It seems some folks, IVIG, and higher doses of Nplate, is about all they (row 4) respond to.
pdsa.org/discussion-group/search.html?searchuser=sachmo16&exactname=1&searchdate=all&order=dec&childforums=1

Thanks for the info Hal. I have written to Sachmo and hope to get an update.
As for the Prednisone/Promacta combo, I guess I'm still confused on how it is administered; i.e. while they tapered down from 25 mg. of Pred to 5 mg, wouldn't they then have to start the regimen over again (with 25 mg) to keep it going? If so, that pretty much gets one's body hooked on Pred dependency and side effects issue (top of which is shutting down the Adrenal glands' production of hormones)?
As for my use of Promacta, I have been on the max 75 mg. does for the past year, with numbers as low as 7K, but usually averaging in the low teens. One of my docs insists that "once effective always effective" applies to Promacta, but the 7K score really got me concerned that this drug is minimally effective in my case, hence the trial Splenectomy, which has apparently failed.

luca wrote: ... One of my docs insists that "once effective always effective" applies to Promacta, but the 7K score really got me concerned that this drug is minimally effective in my case ...

From what I've seen, 'always effective' would be correct. Promacta may look to have become ineffective but what appears to happen is that a second antibody comes into play. Looking at my ITP treatments table. Since you started with a good steroid response that would be a row 1 antibody. Many folks I've seen here also start with row 1 but end up with a row 2 antibody too. Notice that row 2 responds to very few drugs. The good part is that it seems to go into remission easily and often. This is the reason I asked if you had tried steroids with Promacta yet. I would also note that some folks here are on 100mg Promacta. I suspect they are younger, not sure.

Another person that has taken Fostamatinib is user 'jasondema'. Here is his thread.
pdsa.org/discussion-group/7-treatment-general/30100-fostamatinib-low-dose-prednisone-and-high-dose-nplate-triple-therapy.html?start=0#63796
To keep his head above water, he needed an Nplate 10 dose (highest available) AND either regular IVIG or 10-20mg of Pred. He ended up not responding to Fostamatinib alone. As you may know, it is only effective for 18% of the general ITP population.

Because of the week steroid response I wondered if he had row 1 antibody, in addition to the row 4 antibody. Two antibodies being the reason why there was no response. I suggested he take Nplate with Fostamatinib to overcome the row 1 antibody. I couldn't persuade him / his doctor. I would suggest the same thing with you. Probably best to take Promacta and Fostamatinib at the same time.

Hal: I am somewhat confused about your chart, and have several questions. First, if I had a moderate response to Pred. but never tried IVIG, how does that enter in on the chart? Second, you discuss "4 antibodies" but I don't understand how you derived this. Do you have a stream somewhere that explains the basis of the chart and/or any citations you used to figure this out? Third, except for maybe Prednisone and emergency treatments, I have not seen anything in the ITP literature that recommends taking two major treatments at the same time (i.e. Tavalisse and Promacta); can you provide a reference or source? As you suggested to Jasondema, it is going to be a hard sell to both our docs AND the insurance companies to provide both meds at the same time (both of which cost in the $80-100K range!). Finally, back to the chart, if there is some way to identify these 4 antibodies objectively, wouldn't that imply that we should be able to predict the success or failure of a Splenectomy (or other major treatment for that matter)?

luca
I have never had IVIg so don't fit into Hal's chart either. I'm also a firm believer in evidence based medicine rather than conjecture.

Hello All,

Luca...sorry I was not able to get back to you before. I just checked my messages. For me, Fostamatinib did not work. I tried it at 100mg and 150mg and it did nothing for me at all. No response. I paired it with prednisone and NPlate (max dose) and it did nothing. Hopefully, it will do something for you..but at an 18% overall response rate...I think this medication is a long shot for effectiveness.

As for an update on my ITP situation..I went for the indium scan back in September (travel from NYC to London) and my results were a spleen / liver ratio of 3.24 which is showing that the issue is in the spleen. I met with Dr. Provan, who suggested prior to a splenectomy...to do the following:

8 weeks of NPlate max dose + prednisone 15mg daily + Cell Cept 2000 mg daily.........if this fails (which it is because it has been 6 weeks and platelet count still under 30k) then do the following...........8 weeks of Promacta 75 mg to 100 mg daily + prednisone 15mg daily + Cell Cept 2000 mg daily.

The idea is to have the TPO (Promacta or Nplate work with the Cell Cept combo)....If this works..then I can get off of the prednisone. So far, everytime I go below 15 mg of prednisone...my counts begin to drop into the teens.

I am going to Calcutta, India on December 23rd. When I return on January 2nd..we will be switching me from weekly NPlate shots to Promacta. I will be getting an IVIG as a bridge to prevent a platelet crash while I wait for the Promacta to kick in (typically about 2 weeks) as the NPlate rapidly loses its effectiveness.

If this all fails then do the splenectomy in early March.

Thanks for the update Jason. I sent you in another stream my history with the Indium Scan back in 2013, which was highly positive for the spleen (6.14), but nonetheless, my Splenectomy 3 weeks ago failed to help, with my numbers dropping to 4K last week. I can't say I regret having the surgery, which was done by laparoscope, since it finally answered the question as to whether removing the spleen would work for me. As for your situation, like me when the Promacta became less effective (counts in the low teens) I too looked for a backup plan, so I understand your logic and plan. Good luck in your deliberations and hopefully you can find a solution that you can live with...

Hello All,

Another update.....I had 7k platelet count on Friday. They discontinued the level 10 NPlate. I am still on 20mg prednisone daily and 2000mg of Cell Cept daily. IVIG was administered to boost up my platelets and I have been switched over to 75mg of Promacta which I started on Sunday. The IVIG will serve as a 2 week bridge in order for the Promacta to hopefully kick in which will be paired up with my current daily regimen of 20mg prednisone and 2000mg of Cell Cept. Furthmore, I am getting the vaccinations for a pre-splenectomy this coming Friday because me and my hemo both believe the following:

A.) The Promacta probably will not help because I was on it before last year and it did nothing. We are only doing this again because of Dr. Provan's recommendation of pairing it with the Cell Cept.
B.) The Cell Cept is probably ineffective because it has been over 8 weeks of administration and counts are still low.
C.) Indium Scan results favor a higher likelihood of potential success along with my age
(41 yrs old...now or never because the older you are the success rate of this procedure begins to decrease)
D.) Tavalisse failed, NPlate failed, NPlate with prednisone combo failed, Rituximab failed, First round of promacta failed, tapering of Prednisone below 20mg has failed, MMF is looking like a failure, and Dexamethasone and IVIG improve numbers only to come right back down...not sustainable.)
E.) IVIG response is good which can correlate to a potentially good splenectomy outcome based on research reports.
F.) Hemo will not let me try Embril (Etanercept) which has good success albeit limited patient data.

This all leads me to go for a splenectomy because staying on high dose prednisone and IVIG treatments is no way to sustain. I have went through the treatment list without trying (Imuran, Cyclosporine), which can be quite toxic.

I will be on Promacta 75mg for 4 weeks followed by 4 weeks of 100mg of Promacta which will commence at the time of splenectomy (late Feb, early March). The only way I will avoid surgery is if the Promacta provides a sustained response to keep me over 30k with ability to get off of prednisone.

I will keep everyone updated.

Jason: I can truly empathize with the rocky road that you have been on, but there is hope down the road... You may remember that I wrote you 4 weeks ago after my numbers tanked immediately after my splenectomy. I immediately went back on Promacta and my numbers started to surge--weekly counts at 75 mg. went from 4K to 9K, 49k,181k, 291k and 203k (after dosage reduction to 50 mg)! Of course, the MD's are confused about what has happened, but the best explanation so far is that without the spleen, the Promacta is (obviously) far more effective than it had been pre-surgery (my counts on 75 mg pre-surgery were in the low teens to high single digits). So I think that your plan to do the Splenectomy certainly makes sense at this stage of your treatment, and, like you, my Indium Scan also indicated that the spleen was the primary source of platelet destruction.
Two other tidbits to consider; 1) one of my doctors who has a sub-specialty in ITP (Dr. Cataland, Columbus , Ohio) had told me earlier that he has seen it take several months to achieve a stable response to the Splenectomy, so don't be concerned if the numbers are highly erratic afterwards, and 2) Dr. Cataland also states that even though your personal Promacta and/or Nplate response may be limited, he has never seen a drug which has shown some kind of effect completely lose effectiveness in the same individual. So the hope is that once the spleen is removed, hopefully one of those meds will show an increased effectiveness in platelet stimulation activity.

Good Luck and let me know if you have any questions about my Splenectomy experience ( which was more positive than any surgery I have had...).

Jason, on the Indium scan.
You mentioned a spleen / liver ratio of 3.24 before. Was there an 'index of production' value given too?

Hello Hal...
There was no mention of index of production on my scan results.

By the way Hal...check out this link I mentioned in another thread. It is a recent article that indicates those that are likely and not likely to respond to TPO's. Apparently if your serum thrombopoietin levels are high...you will have a less likelihood of responding to the TPO medications. I guess this is something to mention to your hemo so that he or she can check your blood prior to TPO therapy. It could also guide the hemo on what option (if any based on how high the levels are) would be better to start off with. (Nplate or Promacta) based on the results of this blood test.

ash.confex.com/ash/2018/webprogram/Paper117267.html
This paper from December of 2018 (fairly recent) indicates that if your thrombopoietin levels in the blood are above a certain amount...you will have a less likelihood of responding to NPlate (weekly shot) or Promacta (daily pill). The higher the level..the less chance of a response to either drug. The levels for a response are indicated within the paper itself.

Ah yes Jason. I did stumble across that recent article myself. Almost started a new thread on the topic.

Recall that one form of ITP is antibodies against TPO (a fact not mentioned in article). In that case Promacta and Nplate merely replace the missing TPO. In the graphs, I think that reason (replacing TPO) would be the reason why the wide strips thin down to narrow lines. It is always true.

This part at the end stood out for me.
" ... and those with extreme elevations in TPO are unlikely to respond to either agent."
I wished the author(s) would have theorized why that would be true. It's not obvious to me given the information presented or my general knowledge of ITP. My theory as to why though would be that if one's system is producing a lot of TPO then a comparative little amount of Promacta/Nplate isn't going to be adequate. With that theory, my guess would be that you're system is producing a lot of TPO, and, you have no TPO antibody issue at all. Do you have some thoughts on this subject? For the record, I don't think you have a TPO antibody problem or a Liver destruction problem either one.

Oh my. Not responding (at all) to MMF is very much a surprise to me. I would have guessed at least a partial response. The word 'enigma' comes to mind. Blah.

On going back to Promacta. In my mind. If, somehow, you started producing antibodies against Nplate as soon as you started taking it, that would explain going back and trying a higher dose of Promacta.

About the elevated TPO condition, again. After thinking about it, I suppose there could be another mechanism at work to contribute to elevated TPO.

Recall that circulating TPO not only binds to Megakaryocytes but also binds to circulating platelets. This is part of the negative feedback system our bodies have to regulate platelet count. See Wiki for a description. So if there is a drop in Megakaryocyte numbers, because of antibodies against them, that could be an issue. If TPO does not have platelets to attach to, nor Megakaryocytes to attach to, it is reasonable to expect increased circulating TPO. Nothing to attach to.

It would be reasonable to expect Megakaryocyte antibodies to produce the highest level of circulating TPO in ITP. With few Megakaryocytes available, Promacta/Nplate has limited benefit. PDSA user 'drbean7218' is an example of leveraging Cyclosporine and steroid anti-inflammatories to enable effective treatment with a more typical dose of Promacta - 25mg. I think the cost of MMF is prohibitive where he lives and never tried it.

Hal, this is a very interesting theory. But how could we explain my son's situation? IVIG and Prednisone alone had zero effect. Then one dose IVIG plus 60 mg Prednisone together could send his count to 150K plus. Two dose of IVIG and 80 mg Prednisone could send his count to 539K (both time lasted about 2-3 weeks). Then 4 weeks 50 mg Promacta and 4 weeks 75 mg Promacta along with 60-80 mg Prednisone the whole time had zero effect again (started at 10K and ended with 8K last Friday). We will try NPlate this Wednesday and I do not have much hope right now. Maybe our hemo is correct since the beginning. He said this is a strong destruction issue and Rituxan is the way to go. I am totally confused and lost.

th8899 I trust your son has been adhering to the dietary restrictions associated withPromacta (Eltrombopag).
If so it is definitely worth giving N Plate (Romiplostim) a try, it has a slightly different mode of action to Eltrombopag. Romiplostim however is not as easy unless you can inject at home as we do in the UK.

mrsb04, thanks for the info. Yes, we strictly follow dietary restrictions for Promacta. I wake up my son every day at 1 am to make sure it is at least 4 hours after and before any food or drink. I heard a lot of successful story about NPlate after failed Promacta. To my surprise, my hemo told us we could do the injection at home once it worked. We are living in US.

I'm the other way round. NPlate failed me after a year, so I swapped to Promacta 2 years ago. Good news about injecting at home.

th8899 wrote: Hal, this is a very interesting theory. But how could we explain my son's situation? IVIG and Prednisone alone had zero effect.

Looks like typical row 2 response to me. Both row 1 and row 2 are 'strong destruction' issues so I'd agree with your doctor on that one. Row 3 and 4 are production issues.

Then one dose IVIG plus 60 mg Prednisone together could send his count to 150K plus. Two dose of IVIG and 80 mg Prednisone could send his count to 539K (both time lasted about 2-3 weeks).

Yes, to my knowledge, this is unknown behavior. You are first to ever mention/identify it that I know of. It does explain some previous odd behavior of steroid response coming and going, and, IVIG response coming and going. Pat yourself on the back with this one.

Then 4 weeks 50 mg Promacta and 4 weeks 75 mg Promacta along with 60-80 mg Prednisone the whole time had zero effect again (started at 10K and ended with 8K last Friday). We will try NPlate this Wednesday and I do not have much hope right now. Maybe our hemo is correct since the beginning. He said this is a strong destruction issue and Rituxan is the way to go. I am totally confused and lost.

Ok, but really there is little reason to suspect Nplate will not work. Rituxan works occasionally for row 2. Rituxan is a powerful drug though and Nplate is normally benign. Without a steroid response, and thus row 1 response, I'd put Rituxan on the back burner. Nplate and Promacta are notorious for putting row 2 folks into remission.
FWIW, all those that I've seen that take a long time to respond to Promacta (or Nplate) have never been on medium/high doses of steroids. Steroids speeds the normally anemic response of row 2.