variable response to Nplate/Romiplostim

I would be interested in hearing how people responded to nplate (romiplostim), particularly how long it took to get a reasonable result (if at all), and what dose it took to get there. I realise everyone is different and responds differently, but I'm curious to know a) if people took some time to get a response; and b) if people experienced a loss of response, after achieving one.

After a long battle to try it, I first went on Romiplostim 10 weeks ago. From a count of around 20 (only that high because on low dose steroids), I got an amazing response in just one week of a low dose (they thought they were giving me 1 mcg, but actually it was 2mcg..), and a count of 152. Was overjoyed.. Since then the response has been getting lower and lower, even as I up the dose. After 2 or 3 weeks at a certain dose, with falling but still good counts (i.e. above 80) I would crash to below 10, so would increase the dose, and the same thing would happen. Yesterday, after a 2nd week sat 4mcg, my count was just 2, the lowest it has ever been. The doctors have increased it to 6mcg (bigger jump because I need to fly somewhere next week), and I'm waiting to see.

Has anyone else had this problem - i.e. an initial great response, then increasing failure to respond? There are only 2 other people on the drug at my hospital, so they don't really know what to expect. One other woman has been experiencing something similar, and they are thinking of trying it twice a week (lower dose, spread over the week) to see if that helps.

I know that some people took a while to get a good result and stay stable, so I am not giving up hope yet. It was amazing to get a good count and not feel fatigue or dizziness (I get both very badly when the counts are under 10), and I realised just what this ITP has been doing to me over the last 6 years.

I read in the drug info that loss of response should be investigated, and possible causes can be either acquired immunological resistance to the drug itself, or increased fibrosis and reticulin of the bone marrow. Is it too soon to be worrying about either of these?

If it doesn't start working more stably, then I am not sure where to go next. The indium scan showed that a splenectomy would be useless. Perhaps Eltrombopag, now that it has been approved here in the UK. I can get by on low dose steroids (5-10mg) but only just, hovering around a count of 20, and having been off steroids for the last 2 months I really do not want to go back on.

The funny thing is that I've had a similar experience with the other 2 treatments I have tried. Steroids worked immediately and very well (counts shot to 200+) at first, only to taper off over time and just about keep them at a safe level (20+). The same thing happened with Anti-D (WinRho) when it was still available. I had a good response at first, then nothing.

Any similar experiences? Any advice?

Thanks!

Seeing the doctor next week and going to talk to him about getting off the N-Plate and doing the Rituxan again. It lasted 6-8 months and I didn't have any of the side effect like I'm having with the N-Plate. I would rather do 4 weeks in a row and last for a couple of months then going in weekly for CBC and injection. I filled out some paper work online to speed up the process of getting approved for the Rituxan. My plan is to stop the N-Plate and start the Rituxan and I don't know if I can start not next week but the week after on Wednesday am. And I don't know if they will do it in house or at the hospital, either way it doesn't matter with me. I'm sure I'll have to do another round of Dex to get me to that Wednesday.

As you know it took me 7 months to get stable. I think I was lucky partly because I had Dr Provan for a doctor who was always optimistic and partly because I was on a trial so it was a matter of not only seeing what worked for me, but also seeing the trial through. So I just carried on regardless.

I just looked at my records and at week 9 I had a count of 1, at week 15 a count of 9, at week 20 a count of 2, week 21 a count of 1, and even at week 51 I had a count of 8.

Do I thnk people give up too soon? You bet I do!

By the way, they check the blood film for signs of fibrosis each week so you'd know if you had that.

Thanks Ann. I was wondering how many others had had your experience so I thought I would post the question here.

Since you're treated in the biggest ITP centre in the UK, and your doctors see more ITP patients than elsewhere, do you have any idea whether others on the trial, or afterwards, have taken a fair amount of time to stabilise, as you did? Oxford is a major haematology dept, but I'm only the 3rd person they've seen on Romiplostim (including a trial they took part in), and they keep telling me they're learning about it as they go. Fair enough, though given the small numbers on the drug I'd have thought they would have access to the experience of colleagues elsewhere (not just published results of trials, but on-going clinical experience). Otherwise, as you suggest, doctors could just give up too soon.. I've told them I know someone who took months to stabilise, and they look interested, but it's odd the exchange of info is happening at patient level, and not doctor level!

Anyway, a further couple of questions to you (and anyone else!):

- when you went down to below 10, as you report you did several times at first, what did the doctors do, did they raise your dose straight away? And did that usually work at first? Or did you remain on a fairly constant dose but have variable results for a while?

- I was wondering about the fibrosis. I read that to know for sure they have to done a bone marrow exam., but that signs in the blood smear (abnormal red blood cell morphology) can give an indication. Do you know if this is something that comes with the conventional FBC, or is it an extra thing? I'm not aware anyone has been looking at this specifically, though everything on the FBC has been normal so far (except for the platelets!). Which bit tells you there might be an increase in fibrosis? I've had a liver test (though that was my GP who ordered that).

A further comment - this may have nothing to do with Romiplostim, and indeed is not a reported side effect, but since starting it I have had heart palpitations. Could be due to coming off the steroids, I suppose...

Norita,

I started Nplate in January and only got to 24. However, my doctor did not go above 3.7. I also was off of it for a few weeks since insurance would not cover rituxan and Nplate simultaneously. The doctor freaked out and wanted my spleen out in march. I decided to seek a second opinion.

In April I went to Cleveland clinic. I told him I didn't want my spleen out so he upped my Nplate to 5 and put me on cyclosporine based on a study he had read.

Well I have only had 2 drops since then. ( one week my count was over 250 so was not given the dose and following week I was at 4). Another week I was sick which brought me down to 19. They upped my dose and the next week I was at a record high of 365.

The only issue I have had is how all over the place I am ( anywhere from 55-365) so the doc is having to constantly adjust the dose.

norita wrote: Thanks Ann. I was wondering how many others had had your experience so I thought I would post the question here.

From what I've seen here, most don't give it long enough. Hardly anyone seems to get to the 10th dose and gives up long before that.

Since you're treated in the biggest ITP centre in the UK, and your doctors see more ITP patients than elsewhere, do you have any idea whether others on the trial, or afterwards, have taken a fair amount of time to stabilise, as you did?

There were 4 of us on the trial. The other 3 had all had splenectomies so were expected to need a higher dose. One got to the full 10th dose without any response and dropped out. One had a count that went very slowly up and he got to about the 8th dose before he got over 50. Since then he's had to drop the dose a bit because he went high although he's still on quite a high dose as far as I know. The 4th person rarely got a count over 50 but it was thought worthwhile to continue as it kept her over 10. She found that the higher doses gave her terrible headaches so she cut back and found that her count was the same whether she took the high dose or a lower dose. She has recently stopped altogether due to other conflicting health issues.

I've told them I know someone who took months to stabilise, and they look interested, but it's odd the exchange of info is happening at patient level, and not doctor level!

Doctors often seem too proud to ask for advice from another doctor. It's as if they feel their professional worth is threatened if they need help.

- when you went down to below 10, as you report you did several times at first, what did the doctors do, did they raise your dose straight away? And did that usually work at first? Or did you remain on a fairly constant dose but have variable results for a while?

Yes, the trial protocol said if below 50 raise the dose, so we mostly did although not always if my count was over 25. First time, at week 6 I had a count of 9 with mouth bleeding and the other specialist at the hospital said to take prednisolone. I did, but only 10mg for a few days and my count went to over 300. So I refused to take steroids again because it confused things. I also asked that in future they call Dr Provan instead because he was okay with just raising the dose.

My count varied, on 3 mcg/kg my count went 1, 27, 160, 27, 102, 23.

- I was wondering about the fibrosis. I read that to know for sure they have to done a bone marrow exam., but that signs in the blood smear (abnormal red blood cell morphology) can give an indication. Do you know if this is something that comes with the conventional FBC, or is it an extra thing?

It's extra. A blood smear or film is just that, a smear of blood on a microscope slide, stained and viewed. It should be being done each time you have a blood draw. Liver tests aren't necessary on romiplostim although my hospital does them occasionally anyway.

A further comment - this may have nothing to do with Romiplostim, and indeed is not a reported side effect, but since starting it I have had heart palpitations. Could be due to coming off the steroids, I suppose...

Could be. I had an on and off tremor from steroids for a full year after I stopped it. It's a brutal drug.

Thanks. That's very helpful to know.

I don't get the feeling that they're going to give up before reaching the maximum dose, but because I'm supposed to be flying somewhere this week, they want to give me steroids again as well, and a fairly high dose (40mg), which I am not happy about because firstly I hate steroids, and secondly it will interfere with the Romiplostim. I was on 5-10 mg of steroids before starting the Romiplostim, but they think 40mg will get the count up more quickly. They are worried about the pressurised cabin. I've flown with a count of below 20 several times before, but I suppose a count of 2 is slightly different.

It's strange because this time I have not had the crushing tiredness. Low counts *always* made me absolutely shattered before, so much so that I would sleep for hours during the day. I've just got a lot of peticchiae on my hands and stomach, and one or two small, faint bruises. ITP is so weird.

I don't think they have been doing a check on fibrosis. Would that involve drawing a separate phial of blood, or can they use the same phial to do both tests? It sounds like I need to ask them to do this: I just ask them to do a blood smear to check for signs of fibrosis?

Can't believe how varied the clinical handling of all this is. As you know, I got the wrong dose for 3 weeks before they realised (despite my telling them I thought this was happening).

Doing the blood smear to check for fibrosis would be done with the same vial of blood. So it may be being done but you are not told.

If you know that a lower dose of steroid will work then you could take that. If you only take it for a few days you don't need to taper. Of course it all depends on how long you're going to be away but a few days at any dose and then off as we do with dexamethasone would see you through a few days.

I don't think they are doing a blood smear to check for fibrosis. When I asked the registrar she looked blank and said 'reticulin takes a long time to appear and you only started ROmiplostim a few weeks ago', which I think misses the point. I understood that Romiplostim can cause reticulin/fibrosis fairly quickly. Anyway I need to check with my consultant when he comes back from his hols. So far all the bloods while I've been on the Romiplostim have been done in hte Day Unit, and he hasn't had anything to do with them. (We keep in touch via email with reports about doses and counts).

Having issues here in Norway... The higher dose did the trick and my count went up to 141, then I started on the half dose twice a week, and in a week it has gone from 141 > 72 > 22. Very pesky all of this... I thought Romiplostim was going to be the bees knees.

Ann, you say your counts bounced around a lot at first on Romiplostim, but in my case they're not exactly bouncing in a random way. They're shooting up when I increase the dose, then they're falling, and at a certain point I will reach the maximum dose (up to 6 mcg so far). It's like my body cottons on to the drug and starts to resist it, each time I raise the dose. I think I'd prefer a more random bouncing around, because at least that might mean it could eventually settle in a good place. As it is, I just feel my body is trying to do one better than whatever I try and treat it with!

But I shall stick with it for a while, if I can, because when it does work, even only with a count of 20, I feel much much better, and not exhausted all the time, and to be honest that has always been the worst part of ITP for me (aside from the vague, omnipresent fear of a serious bleed).