Chemo vs b-cell depletion

Hi, Anyone have any thoughts about Ofatumumab (B-cell depletion) and Cytoxan (chemo) for vanquishing ITP for good (or at least for a few years)? Think one is better than the other and why?

If you're interested, here's a bit of my treatment history: I had received a series of Cytoxan (euro-Lupus) last summer/fall and it gave me a lot of life back. However, since I couldn't tolerate the Cellcept, I had no maintenance medication and so began to slide backwards again. I am currently doing another series of Cytoxan. Previously had three doses of Ofatumumab, but stopped because it caused more fatigue and pain. I have received Rituxan in the past (many years ago) and after my first infusions it was amazing! I felt all the inflammation in my body disappear. So, unfortunately, I was hoping I would have the same experience with the Ofatumumab. Instead I had increased fatigue and pain and wasn't able to be as active as I had been. I felt as if I was sliding backwards faster, which is always disheartening. (I have since realized that comparing remembered results or feelings is never good)

Amazingly soon after starting the Cytoxan my platelets were holding longer. I think I went two or three weeks without Nplate. (Usually need it every week) My doctor and I don't know if this was due to the Ofatumumab or not, but decided to stay the course with Cytoxan.

I had forgotten how tough Cytoxan can be. It usually takes about a week for me to find some internal balance and emerge out of the darkness it causes. Unfortunately, the Cytoxan seems to be rougher on me this time around. I've had more difficulty breathing and some heart palpitations. Of course, it's hard to know what should be of concern and what to just push through. I'm willing to push through if this is going to help in the long run. (Yes, will be emailing my doctor regarding this tomorrow) I'm wondering if perhaps going back to the Ofatumumab would be a good decision or not. Looking back, the side effects weren't as bad as those from the Cytoxan. Though I could be feeling that because right now I'm dealing with Cytoxan side effects...

At times, it's really difficult separating everything and having an intelligent perspective on one's health and treatment. The urgency I feel to have something put the ITP into remission along with the discomfort of treatment side effects has created a lot of tension in me lately. This has been making it difficult to see and difficult to stay the course. Hopefully, someone can see better than I can right now, or perhaps has had a similar experience. If not, I'll find my way through this. We always do, right?

Thank you

Well, first, there is a big difference between Cytoxan and Ofatumumab as you probably know. One is chemo, one is not. If I had to choose one, I'd probably go with the monoclonal antibody. Cytoxan can have some pretty bad permanent side effects. If Rituxan worked well for you before, why not use it again?

Thanks Sandi. Well, I forgot to include that Rituxan worked great for SLE the first time and the second time I had what could have been a delayed serum sickness. It may not have been, but was severe enough that I haven't taken Rituxan since. Both times I received the Rituxan it was for SLE. Back then the ITP wasn't the problem that it is now.

Emailed my doctor today and asked if he thought going back to the Ofatumumab would be a good choice.

Do you know of instances where people have gone into remission with either a mab or chemo?

I went into remission from Rituxan, but had serum sickness twice (long story). The last time I had it was 2005 and counts have been good since. If you did in fact have serum sickness from Rituxan, you probably shouldn't use any mab, especially one that uses mouse cells. That is what causes the hypersensitivity.

I only know of two people here that had ITP remission from Cytoxan. It isn't used often, but others have tried and didn't have much luck. What else have you tied and how are your counts?

I go for my first Rituxan treatment on Thursday. I'm a little nervous, but from what I've read here, it should be no big deal.

Hi Moe,
I understand the nervousness and fear; completely sane emotions, as are all the other emotions and thoughts you may be having. I will be thinking of you on Thursday. Will you be going by yourself or will someone be going with you?

If you can, talk to your nurse before, or as they are hooking you up. They will be very attentive, especially since it is your first time taking Rituxan. You will be cared for.

And, hopefully the Rituxan will be helpful. I hope so.

Take good care of yourself after the infusion and, when you are ready, please let us know how it goes.

Sandi,

Serum sickness twice! That sounds really rough. However, it's great that you were able to achieve remission with Rituxan. Remission since 2005 is great! I hope it continues.

Yes, I've been staying away from the mouse cells.

For the typical ITP medications, I have taken IVIg, Promacta and Nplate. IVIg, works in emergencies but isn't great as a maintenance drug for me. It doesn't raise my platelets much and doesn't last very long, maybe a week. I tried promacta, struggled with side effects and counts stayed at or around zero, so quit. Nplate works. However, if I don't take it every week (every once in a while can skip a week) platelets drop to zero.

I've also taken Rapamune, which seemed to help for a while and then didn't. Cytoxan, didn't help the ITP last time but maybe this time? I didn't finish the series of Ofatumumab.

If Cytoxan didn't help the last time, it's unlikely that it would this time. Benefit vs risk.
Have you ever tried Win-Rho? It's not used often any more, but some people responded well and were able to go months before treating again.

Yes, I agree with you about the Cytoxan. However, I am taking it for the SLE and hoping it also helps with the ITP.

I have not tried Win-Rho. I just did a quick internet search and will ask my hematologist what her thoughts are. I think I will be seeing her soon. Thank you. I'd be happy to have a month without any medical appointments. I haven't had that in years.

As I understand 'packh1@yahoo.com' has taken both Rituxan and Cytoxin and achieved long remissions with each. This evidence suggests that those with a row 1 response in my treatments table, can achieve remission with either drug. Of course, lots of folks have taken Rituxan and the user success association with row 1 is strong with that drug.

Speaking of other drugs, user 'julia' (also row 1 response) achieved remission using the drug Azathioprine (aka Imuran). It should be noted that the side effects seem to be lower with it than Cytoxin, as described here:
"How I treat idiopathic thrombocytopenic purpura (ITP)"
www.bloodjournal.org/content/106/7/2244?sso-checked=true
"
Our preference is to use azathioprine (2 mg/kg orally every day adjusted to avoid severe neutropenia), preferably in combination with danazol (10-15 mg/kg/d), typically 600-800 mg per day, as the first approach to chronic immunosuppression because the incidence of acute and serious side effects is lower than with cyclophosphamide and the frequency of lasting remissions is comparable (20%-40%)
"
I think Azathioprine can help with SLE too. Not sure.

As a very experienced renal nurse I would urge caution when using Cyclosporine.
It is known to be nephrotoxic.
I suggest you get your kidney function checked before you contemplate taking it.
If you take it then grapefruits & grapefruit juice will be banned from your diet as they increase plasma concentrations.

mrsb,

Cyclosporine? Do you mean Cyclophosphamide?

Thanks for the concern. Yes, grapefruit is often found on the "do not eat or drink" list for many medications.

Sandi, I apologize. I just looked back at my notes and Cytoxan did help with the ITP. It just didn't help enough, but did allow me to skip a week here and there. Sorry, my brain has been a bit foggy lately...

Cytoxan is such a strong drug for ITP, or any autoimmune disorder for that matter. I've done the immunosuppressants for Lupus...Imuran, CellCept and Methotrexate injections. That was as far as I was willing to go though. All of them only caused more problems and didn't help one bit. I'm done with all of that.

b2h...
Yes I'm sorry I did, I'd just got out of bed and was probably 3/4 asleep.
However (in my defence) it applies to both of them.

I hear you Sandi. They are very toxic. After all Cytoxan (and other chemos) is derived from mustard gas, so.... For me, the cytoxan infusions last year gave me back a lot of life. I'm really grateful for that. Unfortunately, one medication doesn't work the same forever. This time around I don't think I'm tolerating the Cytoxan very well, though it may also be helping. I am going to talk to my doctors this coming week and will figure out a different treatment plan.

Wow, thank you Hal! I've been waiting to send you a proper reply, but I think it will take me a bit to read things over, compare notes, talk to my doctors... So, am thanking you now for the thoughtful and informative response.

Hi Hal, I know this is an incredibly late reply. I apologize.
I had some questions about your chart. If I go by the IVIg reaction I would be in rows 2a, 2b and 4, so liver and possibly bone. However you have Promacta as effective treatments and for possible remission in rows 2a and 2b. Promacta did not help me at all. Nplate has worked well. Is there something I am missing in your chart? Thank you

b2h, the table doesn't really give guidance on how to handle multiple antibodies. Can you describe your IVIG and steroid responses?

As far as Promacta. It's either Promacta or Nplate. Whichever works for you.

Okay, thanks.

IVIg works, raises counts to 80-90 or sometimes only to the 40 range, but then within 2-3 weeks I’m back in the single digits. So, in an emergency it’s an option, but as ongoing treatment, it is not.

I don’t recall when I took steroids for ITP, but after my initial hospitalization for ITP and IVIg treatments, I’m sure it was tried. I don’t think it worked that well because I was hospitalized again with single digit counts later that year. I can’t tolerate steroids anymore, so no longer take them.

I do recall rapamune helped keep counts in the safe range, but then it stopped working.

b2h, that IVIG 80 to 90 count would be way to high for row 2. That sounds more like row 4. Do you know what dose of Nplate you are taking?
About Rapamune. When it worked, do you recall what count numbers you were getting with it?

Ah, I see you have clearly put the definitions of poor and weak responses in your document. I apologize. Thank you for your kindness and patience.

My Nplate dose has always been 1 mcg/kg. Nplate injection is every 1-3 weeks.

For rapamune, I want to say an average of 70. Looking back I see numbers ranging from single digits to 130. Mostly, I think it kept me in the 40-50 range. I was taking other things then as well and was in the hospital a few times for reasons other than ITP. There was a period when I was taking a combination of decadron and rapamune and I believe that is why my counts were above 80 during that time. I don’t recall why that didn’t last. Anyway, the rapamune kept me safe.

A couple of years ago my platelets dropped to single digits and wanted to stay at zero, so I was hospitalized a few times. This is when I knew the rapamune was no longer helping with platelet counts and since it wasn’t helping with anything else either, I discontinued it. Shortly after I began Nplate.

Why did you put a question mark next to bone in row 4? Do you think it’s a combination of bone marrow and perhaps liver and/or spleen?

Oh wow, that is next to nothing for Nplate. I see why you were thinking row 2 now. Partial remission maybe? Are your counts acting like they are trying to hover in the 40 to 60 range - hence skipping Nplate some weeks?

On the IVIG again. Were you taking steroids or something with IVIG for those 80-90 counts? Or, maybe when you were first diagnosed?
When the Rapamune failed. Did they give you IVIG then and at that time did the IVIG not do well?

On row 4. I did the table a year ago. All the question marks indicate something I was unsure about at the time. It now appears that 'megakarocytes' would be the appropriate term.

I have a good hematologist. She doesn’t freak out and started me on the lowest dose Nplate and has kept me there.

Counts want to go to zero. Cytoxan and Arzerra have helped. Without those, it’s Nplate every week. I’m still hoping for remission, but getting to a point where treatment is needed only once a month would be great.

I think for a time it was IVIg (hospital), Rapamune and Decadron. Counts reached 100’s for maybe about a month. With Rapamune and decadron I made it past 60, which for a while I couldn’t get past. I was usually in the teens to 40’s with just Rapamune. Then I did Benlysta (still on Rapamune too) for a bit. After the 5th infusion counts went to 100’s from the 40-ish range. I only did six Benlysta infusions. They didn’t help (though maybe helped platelets) and increasingly had more and more side effects. After the sixth infusion, platelet counts were okay for about six months, then single digits again. Started Rapamune again and went back to low, but safe counts. Stopped Rapamune, and about two months later single digits. Rapamune didn’t help again. Multiple hospitalizations and then Nplate.

I’ve had IVIg off and on since when I was first diagnosed. It’s the emergency drug for me. It’s what I’m given when I end up in the ER. I did try to use it as maintenance, but it just doesn’t give me great results. An all day infusion for safe counts that only last a week, possibly two, just isn’t worth it. IVIg response has always been the same. In the ER it's great, but I need a lot and my response doesn't last nor do I reach really high counts.

Megakarocytes makes sense. I think for me it’s a combination of low production and destruction. My bone marrow is a bit hypoplastic.

A while ago I read and was told that ITP is not progressive, but recently I read an article that called ITP a progressive disease. What do you think? For me, it seems it has been progressive.

I've never thought as ITP as progressive and have not really seen that here. Some go into remission and some struggle along with the same counts/treatments for years. Occasionally, there are people who seem to be less responsive to treatments as time goes on, but that is not the majority or even close to half.

Were you doing Benlysta for ITP?

Thanks Sandi.

Benlysta was for SLE. There were many other medications over the years, but am only listing the main ones.

Ok. That makes sense.

That is quite a story b2h. Why the hold back on the Nplate dose? Because bone is a bit bypoplastic?

I don't really have anything on ITP being progressive - though I do remember 'rjsmyth' commenting his IVIG response was worse after Nplate. It does seem reasonable to expect it getting marginally worse very slowly with age.

Thanks Hal. ITP certainly has taken all of us on some interesting journeys. I’m fortunate I respond well to Nplate. The low dose works for me. With that dose, I stay well (as long as I go for regular injections) and counts never go over 200. I’ve never experienced the large swings in counts that I so often read about.

Interesting about rjsmyth writing about his ITP worsening after Nplate. I read some of his postings and read that Nplate stopped working for him after about 2.5 years. I’ve read that has been the case with others as well. (Think the search is limited, can’t see all postings, so didn’t find the one about his ITP worsening, but that’s okay)

I feel my ITP gradually worsened prior to the Nplate. It didn’t use to be so stubbornly focused on zero. Past few years, it has been. Of course there are so many things to take into consideration and who knows how everything relates to everything else, so could be that it feels it’s been progressive, but really is not.

b2h, you mentioned taking Nplate every 1 to 3 weeks earlier. On weeks that you skip Nplate, what is your counts at that time?

I have no idea. I generally don't go for labs if I don't go for treatment. I schedule my own treatment, so go when I feel I need to.

Just a clarification: I know I wrote that my counts haven't been higher than 200. I meant that when I have gone for labs they haven't been. I am assuming they have been over 200 with Nplate because the number of platelets that I can lose in a week is pretty high.