High-dose dexamethasone and rituximab

I am curious whether anyone here has had the Rituxan treatment combined with high dose dexamethasone "HDD" pulse (40 mg/day X 4 days). The combination shows up in the literature as possibly improving the results of Rituxan.

Ellen has started along that route (and using the 100 mg low-dose Rituxan), but I am not aware of anyone else here who has tried it recently. I am curious what results others may have had. I did see earlier posts that were unsuccessful, and other posts where we never learned the outcomes. Have there been any success stories?

Dean, you mentioned that you were given dexamethasone, but didn't indicate whether it was the HDD pulse.

When I had dexamethasone it was prior to receiving platelet transfusions when my counts were under 10k. It was fed through an IV pump. Not sure if same as HDD pulse. I started 1 of 4 Rituxan treatments last Thr along with 2 IVIG treatments this past Mon and Tue. Count is 134k now.

I'm surprised we don't see more of it, Rob. The remission success rate seems pretty high.

I specifically asked my haemo for this in June last year. I decided that if I were to consider rituxan then it would be in this way due to the higer & longer remission rates. He point blank refused. I even had the research article with me. This led me to refuse rituxan & I tried mycophenylate instead - which didn't work btw.

He thought it was too much to put my body through at once. I disagreed but went with his decision because I'd only tried pred & ivig at that point & he made some strong arguments for the mycophenylate.

I really hope it works out for you & Ellen. The research looks pretty convincing. Good luck!

I think it probably is a lot to put your body through all at once but I've seen much worse. I'd do it for a shot at a longer remission. Even if you'd get three years from it, it's better than trying Prednisone for months, then trying Rituxan, then trying Dex, then splenectomy and everything else for years like many people do. Especially you since you want a shot at conceiving. It's too bad he wouldn't go for it.

The papers I've seen don't actually claim that rituxan works better with the steroid but that the steroid works with better with the rituxam. Subtle difference but very real.

Ann, there was one that came out a few weeks ago that that did say Rituxan is more successful with Dex. I'll try to dig it up later (if I remember)!

Ann, I am familiar with the studies, especially the one by Zaja, that were framed the way you described, and you are correct about those... in fact I made the same comment at the time they were posted. However, I have come across other studies that suggest that the reverse may also be true, that rituximab plus high-dose dexamethasone (HDD) is more effective than Rituxan alone.

The summary of seven studies of low-dose Rituxan, that I posted earlier, comprised roughly 200 patients, half of them with and half without HDD. These studies need proper meta-analysis, but they appear to show better results when the combination is given. Here is the link:
pdsa.org/forum-sp-534/7-treatment-general/27993-low-dose-rituximab-rituxan-research.html?limitstart=0#40513

Sandi, is this the one? I think I will cross-post it under new articles:
A recent study demonstrates improved results with a combination of standard-dose rituximab (weekly x 4) and usually 3 4-day cycles of 28mg/m2 (max. 40mg) dex at 2-week intervals (R+3Dex).

Rituximab Combined With Three Cycles Of High Dose Dexamethasone Provides a Long Term Response Rate Similar To That Of Splenectomy In Patients With Immune Thrombocytopenia (ITP) Of Duration Less Than 2 Years

Conclusions R+3Dex provides clearly superior results to rituximab alone. Notably, there was a 75% response rate overall (50/67 pts) compared to 50% with R alone. The 5 year response rate was almost 50% of all patients and 3/5 of responders. In patients who had had ITP for ≤ 2 years, the response is comparable to what has been reported with splenectomy.

www.bloodjournal.org/content/122/21/2310

Thanks, Rob! Saved me time.

Saved me time?

That phrase sounds funny to me right now, like something Popeye would say.

Shiver me timbers!

The last study mentions "The 21% rate of hypogammaglobulinemia".
Does anyone know how dangerous this might be?

Hi Rob, I joined PDSA and go in for my 1st rituximab infusion this Thursday. I was researching HDD as well and my Dr. recommends it. I was diagnosed last July at 13 and have been taking prednisone since. After tapering to 10mg 2x/week I dropped to 28, then went to 10 mg 1x/day and have been hovering around 30 since which is I decided to do the infusion. I was wondering if other than what you've already posted which was VERY helpful if you have any other information about the Rit/HDD combo, whether you found out was what the 22% rate of hypogammaglobulinemia meant and if there is more on how many cycles of HDD was optimal in studies?

Thank you very much!!
Mike

Excellent questions, Michael.

I should warn you that there are huge individual differences in how people react to HDD. Some find it preferable to prednisone because it is over with quickly... like pulling off a bandaid. Others find HDD to be very difficult to handle. You should read this thread in its entirety:
pdsa.org/forum-sp-534/7-treatment-general/27806-prednisone-versus-high-dose-dexamethasone.html

In that thread I wrote the following:
From what I have read and what I have observed, I would try 4 courses of HD-DXM before ANY other treatment, unless the side effects proved unbearable.
I still feel that way, that if you can tolerate the HDD well, 4 pulses of HDD seems to do as well as Rituxan + HDD. Without the added cost. Without the added risk.
www.bloodjournal.org/content/109/4/1401.full?sso-checked=true


I am curious, does your Dr. recommend the HDD/Rituxan combination, or just each treatment separately? Most doctors are not using HDD, and yours would be only the second I have heard of (other than in the literature) to use the combination.

There has been research with 4 x 100 mg low-dose rituximab combined with two pulses of 4 X 40 mg dexamethasone that also got very good results. I don't think that there is enough data to compare one dosing scheme with another, except to say that it has clearly been shown that the combination works better than either drug working separately (when HDD is given for just one cycle). What has not been studied at all is whether giving the drugs together is any better than giving one drug, and if that doesn't work trying the other. In other words, we don't know if their action is synergistic or incremental.

I have not learned anything more on the hypogammaglobulinemia, but it does tell us that the immune system is temporarily impaired. My wife, Ellen, did the low dose Rituxan with the high dose dexamethasone, has had no unusual infections, and has had a partial response (meaning that her platelets are not in the normal range but have remained above the treatment threshold), since August of last year.

Hi Rob and thanks so much for your comprehensive response.

To you question, I actually approached my Dr. after reading the studies about Rit/HDD and he said he was familiar with them, written by a renown ITP specialist but was not sure why it didn't progress from phase 2 to 3 trials (his words, I haven't had time to validate). He was amenable to doing a 1x HDD pulse after my first infusion next week with a taper of prednisone to 10mg every other day for a short time (then discontinue altogether). I'll ask more questions about how many cycles he feels would be appropriate. After reading your link below I wish I would have started on HD-DXM.

I've reacted well to prednisone when originally on 60 mg/day right after diagnosis so hopefully the same will be true for HDD if I decide to do it. Fortunately for me I have good insurance with Kaiser so my infusions are covered by the co-pay. I assume I'll be taking 375 mg x 4 and not the low dose but I'll find out tomorrow.

I kind of figured the hypogammaglobulinemia had to do with immunity suppression given the infusion is a form of chemotherapy. I'll ask my Dr. if I need to take additional precautions.

I only hope I can go into CR or PR like your wife has. Thanks again for your support and advise.

My wife works with AIDS patients in an infectious disease clinic, with every opportunistic infection imaginable floating around; but her hematologist did not advise any extra precautions. Still, it makes me nervous, especially when she was on both Rituxan and dexamethasone. So far, so good.

Michael:

Rituxan is not really chemotherapy, it is a biological treatment like Enbrel, Humira and Remicade. It is an immunosuppressant, but most people do fine as far as infections following treatments. A lot also depends on other medications that may have been used prior to or during Rituxan.

The low dose Rituxan isn't necessarily done to save costs. Studies have shown that the lower dose can be just as effective as the higher dose for ITP. Lower dose is used to reduce toxicity exposure.