Low dose Rituximab (Rituxan) research

Interesting. But it may not be useful for ITP. It talks of B cells being depleted *enough* for 6 weeks for MS. The 'enough' for MS may not be nearly 'enough' for ITP although I agree that we only do 4 infusions because it's 'always been done that way'. Much more study needs to be done. The reason it hasn't been done to date is probably because the drug is used off-label for ITP, as are all other drugs except the TPOs.

(By the way it's 375 per metre squared and not per kg.}

Ann, agreed that much more study would need to be done before official dosing recommendations could change, but....the article I found certainly gives us a new bookend at the low end. Using a dose that has been effective for MS is possibly just as valid a strategy as using a dose that is considered "maximally tolerated" and has been used to combat CLL and NHL.

I know the research will probably never be done now, but I suspect my hematologist would look at the "data" and agree to try a single dose of 100 mg, or spread 4 doses of 100 mg over a much longer time if I asked.

My friend had 8 doses - been in a great remission ever since. Can't remember when this was done - maybe 2006 or 2007. Didn't it start out that 8 infusions were given, not 4?

I may be repeating what Ann said, but stating it differently. The standard dose regimen of rituximab depletes B cells for about a year. The single dose of 100 mg depletes B-cells for about six weeks, but the effect seems to last much longer, according to the author, when looking at MS. But, the minimal dose may deplete B cells long enough for a lasting effect with MS, and still might not long enough for a lasting effect with ITP.

Interestingly, even if 100 mg were needed every six weeks, it would take an average of three years to use as much rituximab as in one standard dose series.

There is another way by which this study may not be applicable to ITP. Rituxan not only depletes B-cells. It also has a beneficial effect on T-cells, especially by increasing the numbers of Treg cells which help modulate the immune system. The minimal dose may be adequate to deplete B-cells, but it might not be adequate to have the desired effect on T-cells.

I agree it warrants further research, and being a "guinea pig" bears little risk except having to repeat treatment at a sooner date. Even if more frequent treatment is required, single dose treatment "as needed" might be a more cost-effective and less risky approach than other dosage regimens, perhaps even the 4 X 100 mg regimen.

If I were conducting such a study, I would treat two ITP groups, one with 1 X 100 mg, and the other with 4 X 100 mg, and repeat treatment as needed to maintain platelets above a specified threshold, perhaps 50k as that is the "partial response" threshold for most previous studies. Then I would compare total consumption of rituximab as well as adverse reactions, between the two groups.

I don't think the article said that 100mg completely depleted the B cells, I think they said that it partially depeleted the B cells and that is why I wonder whether a single dose of 100mg would be enough for ITP. Of course we don't know but it may be that total depletion is necessary. That is what I think I was trying to say!

Oh, and I'm not sure I'd want to be a part of a research program that necessitated taking a drug with a black box warning every six weeks. I think you'd find it difficult to find the participants which is maybe one reason why most studies on Rituxan are those that use historical information.

You are right, we are saying something different.

We observed a near complete reduction of CD19+ lymphocytes (0–0.6%) at 2 weeks, and this effect persisted for a period of 6 weeks (0–0.5%).

I assumed this means there was nearly complete depletion of B cells since CD19+ is just a way of counting B cells. Am I understanding this incorrectly? I am pushing the envelope of my understanding of this topic.

My take on this article is that the author was concerned with the persistence(duration) of the depletion, not the completeness of it, and whether a six-week B cell depletion might be able to give a longer term positive effect on inflammation.

Although persistent B-cell depletion is desired in NHL, it remains unclear whether this is safe or necessary for sustained clinical efficacy in inflammatory diseases.

Some ITP Rituxan users get results that last long beyond the recovery of B cell levels. If the same is true at the minimal dosage, then we are not talking about retreating every six weeks. My every-six-weeks comment was an "even-if" argument, stated poorly.

Melinda wrote: My friend had 8 doses - been in a great remission ever since. Can't remember when this was done - maybe 2006 or 2007. Didn't it start out that 8 infusions were given, not 4?

No, to my knowledge, 8 infusions were never standard for ITP. I first had it back in 2002 or 2003, one of the few who'd had it here at the time. This was back when Ron had the 'Rituxan Scoreboard' going. Anyone remember that? His wife was one of the first in the US to use Rituxan for ITP. Because of Ron and his wife, I brought it up to my Hemo. Ron only ever spoke of 4 infusions. After all of these years, only the odd person here and there has had 8 and I think that is overkill. If B cells are generally depleted after 4 infusions (or two) or whatever they say now, there is no reason for more of the drug. That's like saying, "okay, you get a good response to 60 mg's of Prednisone, but we're going to give you 120 mg's". Unnecessary toxicity.

Since Rituxan can take 4 to 12 weeks to kick in, it's possible that your friend would have a response at week 8 regardless of how many infusions she had. Everyone responds at a different time rate. I've been in remission since my one lonely infusion in 2003 or 2004.

People seem to respond so differently to Rituxan that you can't possibly know how how any one person would have responded with a lower dose or number of infusions than what they had.

Thanks Sandi - I thought 8 was the norm at first. Know that's what my friend had. Boy do I ever remember Ron's scoreboard, good guy!

I remember finding this blog post in 2006-2007. It's got a good plain-English description of how rituximab works. I have no idea if the CD20 shaving caused by excess rituximab is of concern in ITP or other autoimmune conditions, but it is, to me, a good reminder that more is not always better.

clltopics.org/SponsoredProjects/RituxanShaving.htm

Rob16 wrote:
There is another way by which this study may not be applicable to ITP. Rituxan not only depletes B-cells. It also has a beneficial effect on T-cells, especially by increasing the numbers of Treg cells which help modulate the immune system. The minimal dose may be adequate to deplete B-cells, but it might not be adequate to have the desired effect on T-cells.

We're all just postulating here, so I'll just add another nugget. MS has long been considered a T-cell mediated autoimmune disease, and I think that's one of the reasons rituxan wasn't tried earlier for MS. I think rituxan's affect on t-cells is a relatively recent discovery (I bet John Semple had something to do with it).

Sandi-

Yes, I remember the Rituxan score card. That and Ron's posts really helped me feel more confident when my dr wanted me to try rituxan.

Interesting article, Tamar. Makes you think. There is a lot of research that claims that that sort of 'garbage' in the body can contribute to inflammation and connective tissue disorders.

Thanks for the article on CD20 shaving, Tamar.

I followed the link to the clinical trial site and read that the trial was complete but not yet reported. Any news on the results of the trial?

Hey was there not someone years ago on the last forum keeping track of people's responses to Rituxan?

Sandi maybe you remember?

Ha ha, yes. I mentioned it up above. Ron's Scoreboard.

Duh I just reread! Sorry work nights so midday is not my best brain function lol!

hi Sandy , i'm back again since 2011 . my son tried rituxan and he was in remsion for 2 years , unfortuntly his platlets dropped last month ,back to the hospital ,ivig again for 7k count ,
can my son try rituxan again ? and it could work for him again ? i don't knwo i'm so deppresed

Hello Farida! How are you? I'm so glad to hear that your son finally did have remission. Yes, he can try Rituxan again and there is every reason to believe it will work. Try not to be too upset, hopefully this is just a temporary set back. Some people do even better after a second round of Rituxan than they did after the first.

thank you sandi , his count was 500k last week ,im wondring why they crashed very quick , yes sandi rmember he will graduate from university next month . i thank God sandi but i'm a mom i wanted to see him happy all the time .

Well that was not true in my case. I did the full dose 4 weeks and had a great 4 1/2 year remission. Again I had the full dose 4 week treatment and I relapsed after 18 months- still a great response but not as good as the first time.



Farida
I have had 3 rounds of rituxan over the last 7 years. I got a good response each time. If your son responded well the first time, that is a good sign that it would work again.

yes he did, but he got 375mg for 4 weeks , i'm worry if he takes the 100 mg and it dosn't work .
shall we ask his doctor to give him 375 mg or go with the low dose ,

Can you ask the doctor if he has read the studies about the lower dose? If he has then he can decide whether it would be a good idea to try the low dose.

i think he did , but i didn't and i can't read it now ,so tired from reading researcher ,i'm not in a good mode to read anything ,but if i got a summery about that research i will appreciated .
thanks for your reply

Farida, does this summary from page one of this thread help?
www.pdsa.org/forum-sp-534/7-treatment-general/27993-low-dose-rituximab-rituxan-research.html#40513

Rob i read that on the first page of this article , but i'm not a doctor to decide for my son , i don't like to take any risk ,his doctor didn't give advice , he told him if you want to take the low dose i'm ok with that , it seems like nobody knows ,everyone respond differently.

Farida, you must either do the research to make the decision...or trust the doctor to make the decision.


We are not doctors and we only each have a single experience to share. None of us know what the "perfect" dose of rixubimab is, and neither do the doctors. You much choose what you are comfortable with after understanding the pros and cons, only some of which are discussed in this thread (the ones we in this discussion know about).

Hi sandi
my son done with 4 infusion last week , his count is up with corizon ,but once he stopped it , dropped down ,doctor put him back on cortizon . my son stoped it by himselef .
last count was 20k wiht 20mg predinsone, yesterday was his 4 th week , he got the low dose ,i don't know if it will work for him or not , doctor said he can give him more infusion , since what he got is equale one dose 400 mg , i don't know .i think i should wait and see.

In the Zaja study mentioned earlier, "The median time to response and time to complete response were 31 and 44 days respectively." This means that HALF of the patients took MORE than 30 days to respond at all. One patient took 90 days to reach a complete response. I think you are right that you should wait and see.

thirty days from when ? when he finished the last dose or from day one when he start the first dose

I always assumed it was from the first dose, but hopefully someone else knows for sure.