Maintenance Rituxan - Thoughts?

Hi All,

I was diagnosed with ITP in May 1998, and then had a bout with TTP in October 1998. Following hospitalization and plasmapheresis, my platelet count remained stable in the 80-90K range for 15 years. Then, last summer, my counts dropped to 21 and I was restarted on Prednisone. Of course, I did not respond to the steroids and so, during the month of October 2013, I did 4 rounds of Rituxan infusions.

It took a while for my counts to stabilize from Rituxan (around January 2014) and I remained on low dose Prednisone until July 2014 (I tapered all the way down to 2.5 mg every other day for the months of June and July). My monthly platelet count in August 2014 was 121.

In late September, I developed extremely heavy bleeding during my menses and noticed blood blisters in the back of my mouth. I went for a CBC and my platelet count had crashed to 6K - the lowest my count has ever been.

I was sent immediately for IVIG (never had this before and never will again - the headache I developed for a week post infusion was the worst I've ever had) which raised my count to 39 (temporarily) and I restarted Prednisone 60 mg. I also started Rituxan again - had my second infusion this past Friday. My platelet count at this point remains low at 10K.

My hematologist has now recommended I do "maintenance" Rituxan (assuming I respond well to it again this time). He ordered this protocol for a patient who had recurrent TTP and the maintenance Rituxan put this patient in a long remission. He thinks it could have the same effect for me. Basically, I would get the (4) Rituxan infusions every 3 months for a year.

Any thoughts on this? My hematologist is very concerned over my "crash" this time. I have never crashed before. My counts typically fall slowly over the course of many months. And I've never had bleeding like I did this past time. I was bleeding so heavily that I am now anemic and will require an iron infusion after I'm done getting Rituxan. I do not want to risk another crash nor do I want to stay on steroids long term again. And I have refused splenectomy for 16 years and still feel strongly that I do not want to go that route.

Also, Promacta and N-Plate are not viable options for me. I have Lupus, and my ITP is from platelet destruction, not a production issue. My bone marrow is working just fine and producing plenty of platelets, but my body is then destroying them.

I tolerate Rituxan fairly well - although I develop a reaction after the second infusion (rash, fever, joint pain) which is easily treated with a Dex Pulse.

My concern, of course, is what long term effects that much Rituxan can have on my body. I am 36 years old, married, with a 5 year old son. I haven't found any studies that show toxicity for long term Rituxan, although I will continue researching this. And, of course, I will discuss this further when I see my hematologist again in early November after I finish this round of Rituxan.

Any thoughts or insight is welcome.

As always, thank your for your replies.

~Lauren

Lauren:

I'm not even sure where to start. Okay, I'll dive in.

First, didn't you think that you may have had serum sickness the last time from Rituxan? If so, then you should not be doing it again. A serum sickness reaction can get worse each time you are exposed to the drug. I had a second reaction from a second round and it was much worse. I wouldn't count on controlling it with Dex. It can cause analphylaxic shock and if that were to hit in the middle of the night, you'd be in trouble. Because it's a delayed reaction, you don't have any control over when that might happen and serum sickness seems to hit very quickly. It hit me both times in the middle of the night. Everything I've ever read has said that there is no way to prevent serum sickness. I have seen doctor after doctor not take it seriously enough, or they don't believe that Rituxan causes it. It can be a very serious illness.

Second, I am not a fan of Rituxan maintenance. It's a toxic medication and that is also taken too lightly. There are risks that go along with it. Each time a person uses immunosuppressive drugs, they become more susceptible to certain cancers. Pounding your body with those things can be worse than ITP itself. Most people crash at one time or another and that is usually controlled. It doesn't mean it will keep happening and if you fear that, monitor more frequently. Here's the thing about maintenance: A person gets 4 infusions and counts go to 150. So they get maintenance for a year which is 12 more treatments in your case. What if your counts would have just stayed up with the first round? You'd never know that and would have had 12 infusions for nothing. That is a heck of a lot of Rituxan. Newer studies have shown that two infusions, or four lower dose infusions, are getting the same results as the four standard doses. I'm not so sure that more is better. Is your doctor using some sort of protocol for this or is it just his theory?

I had my first round of Rituxan in 2003 and it lasted about a year. I had serum sickness, but it was misdiagnosed so a year later, I wanted to use it again when counts fell. I started it and was hit with serum sickness again, so no more Rituxan for me. That was in 2004 and my counts have been good ever since. If I'd used maintenance, I'd have had all those treatments for nothing and would have given maintenance all the credit.

Last, most people with ITP do also have production problems and that cannot be determined by a bone marrow biopsy. Most doctors are mistaken about that. I wouldn't rule out N-Plate or Promacta just yet.

pdsa.org/forum-sp-534/6-general-itp-discussion/11698-bone-marrow-biopsy-and-production-answers.html

Sorry about the strong opinion. But you asked.

www.news-medical.net/health/What-is-Immunosuppression.aspx

onlinelibrary.wiley.com/enhanced/doi/10.1111/ejh.12102/#author1

My son who is 33 and had recurring ITP and hemolytic anemia since he was 7 is doing a Rituxan maintenance protocol that Dr Bussel [medical advisor for this site} uses for children with ITP. His protocol is different. You get 4 weekly infusions then one infusion every 3 months for a year and every 4 months for the next year for a total of 11. He also gets dexamethasone, I believe with every other treatment. He hopes to get a 6 year remission rather than 4 years he got after just the 4 weekly infusions. He chose to do this treatment because after taking prednisone over 20 years he wants to live at least for a while without having to take any medication or the associated blood tests. He has received 8 infusions so far with no problems. Twelve infusions in one year sounds like an awful lot to me too. Also he had serum sickness before he ever got Rituxan. He was hospitalized for a week. Like Sandi said; you could have a more severe reaction with repeat exposure. I think I would have encouraged my son to try the 2 infusion or 4 lower dose infusions if I knew about those options at the time. I'm sorry you have to be here. Good luck. Joan

That maintenance schedule seems a bit more reasonable. Who am I to go against Dr. Bussel? Using Dex with Rituxan has shown promising results in studies. However, without having any evidence that 16 Rituxan treatments in a year shows promising results and no long term problems, I'm not sure I'd go that route.

Over the years, I have developed a much different stance about treatments. Sometimes, there is treatment overkill. We, and our doctors, pound our bodies with these meds without giving much thought to the possible adverse consequences.

Joan - how is your son getting off of Prednisone after 20 years of it? I can't imagine.

Thank you both.

I appreciate your honest opinions and Sandi, you hit the nail on the head as far as my concerns with Rituxan maintenance.

Joan - I agree with Sandi that the protocol your son is following is more reasonable than the one my hematologist has suggested. I will discuss this further with him in early November at my next appointment.

Sandi - yes, I suspected I had serum sickness after my second infusion of Rituxan last year. Both my hematologist and rheumatologist both feel it was not serum sickness but rather a flare of my lupus, primarily because I tolerated infusions 3 & 4 without incidence. However, I did have residual joint pain in my knees and feet for approximately 6 months after this "flare".

Interestingly, this past Friday, I had my second Rituxan infusion of this round of 4. On Saturday evening, I developed the red rash on my arms and legs and joint paint. I started the Dex Pulse and my symptoms subsided completely within hours. I have no residual joint pain like I did last time. I have no idea whether this reaction is serum sickness or a lupus flare, but it definitely seems to be a pattern for me to have some type of reaction after the 2nd Rituxan infusion.

Also, to note, my rheumatologist suggested maintenance Rituxan last year when my counts were steady in the 120-130K range. At the time, my hematologist and I agreed that my counts were stable and there was no need to treat. I am leaning towards this same plan this time as well. As you mentioned, Sandi, my counts could be stable for a year after this round of Rituxan. I may not need any more infusions to have a decent remission.

Thanks again to both of you. I now have a long list of questions for my doctors.

~Lauren

Lauren:

I guess it would be hard to tell whether you have had serum sickness or a Lupus flare in your case. Dex would help the symptoms of both. They can be very close as far as symptoms. Having had both serum sickness and Lupus flares for sure, I can tell you that there is a huge difference. Serum sickness woke me up in the middle of the night both times and I was practically unable to turn over in bed. It hit hard and fast. I could barely hold a cup to get a drink. Joints were so painful that they felt like broken bones in my entire body. I had a fever, headache, hives, and my skin was red in patches. Lupus flares can be painful in joints, but not quite as bad as serum sickness.

I think I did tell you before that after my first serum sickness episode, I did go on and have another infusion the following week without problems, like you did. That does not prove or disprove serum sickness. The most important thing to do is look at the timing. First time serum sickness with Rituxan - 14 to 21 days after the first infusion. Second time serum sickness with Rituxan - 10 to 14 days after the first infusion. That timing has been consistent for nearly everyone who has had serum sickness with Rituxan. I did not have Lupus when I had Rituxan so I wasn't having a flare.

I was left with residual widespread inflammation that never went away and that was 10 years ago. Wow - 10 years...hard to believe. Anyway, I'd hate to see something like that happen to you. I know that I am sensitive to so many drugs and many Lupus patients are. The side effects can trigger so many problems that just don't go away. My Rheumatologist keeps pushing Imuran and CellCept, but I've been on both before and all they do is cause problems. I just get so fed up with all the drugs they keep pushing that do more harm than good. Lupus patients are more prone to certain cancers as it is, then you add drugs that can cause it on top of that. You have to decide what is really necessary....benefit vs risk.

Please keep me updated on how this goes for you!

Sandi: You asked how my so was getting off Prednisone after 20 years. He was only on continuously for about 16 years. He did fine getting off because the doctor tapered him off very slowly over 16 years down to 2.5 mg every other day! Occasionally he went back up to 10 mg a day if his hemoglobin was dropping but was on less than 5 mg every other day for most of the time. Looking back I'm sure those low doses weren't doing anything. If only I knew then what I know now. At least I didn't let them take out his spleen. The other two times he was tapered " faster" over about a year and a half and did fine........Lauren, hope you are doing well. Keep us updated. Joan

Joan:

16 years is a very long time to be on Prednisone. I've read that after someone has been on it for a long time, there is adrenal insufficiency and the adrenals may not come back to functioning levels. I've been on 10+ mg's for 10 years and know I will never get off of it. Years ago, I tried to taper by 1 mg. every 6 weeks and couldn't do it. I have Lupus though so it's a bit different...my body pretty much shut down. The inflammation was incredible and I felt nearly comatose. My doctor knows that I will never get below 7.5 mg's and won't even ask me to try it. I think I'd hit her with something heavy if she did.

If he's been on less than 5 mg's though, it may be possible. I'm just wondering how hard it's been to taper. Is he having a hard time with it? I'm curious because I've never known anyone to come off of it after so many years.

Hi All,

Time for an update -

This past Friday, I had my 3rd Rituxan infusion. About an hour and a half into the infusion, I developed the chills, my sinuses started draining down my throat so badly that I began coughing uncontrollably, and then I started itching. Within a few minutes, my throat began to swell and I was covered in hives on my wrists, armpits, and legs. The infusion was immediately stopped and I was given an additional 50 mg Benadryl (already had 25 mg at start of the infusion) which did nothing. Then they gave me 125 mg Cortisone - again this did nothing. Finally, they gave me Solu-Medrol, which did clear up the hives and itching, but my throat remained swollen for hours (felt like I had a ball stuck in the back of my throat).

After speaking to my hematologist on the phone (my infusions are done as an outpatient at the hospital, not in my doctor's office), I made the decision NOT to finish the infusion. There was only about 100 mg left in the 500 mg bag of Rituxan and I figured I'd had enough for one day.

I am not planning to have the 4th infusion this week. And clearly, maintenance Rituxan is now off the table as well. I know there are precautions they can take to "desensitize" me prior to infusion, but I've now had 3 reactions to this drug. I've had enough.

I must admit - I felt better a month ago when my platelet count was 6 - then I do now. Yes, I had significant bleeding issues and had to treat - but between the steroids and the Rituxan, I just feel lousy. I have an appointment with my hematologist next Tuesday and we will discuss other treatment options (of which there are fewer and fewer of now).

~Lauren

I was on low dose prednisone for almost 10 years for ITP. I was able to maintain safe counts on a dose of 2.5 to 5 mg per day. I tried to get off of the prednisone many times, but my counts always fell to below 10 within a few months. Finally, after about 9 years, I was taking 2.5 mg and my counts rose to normal levels, so my hematologist called me very excitedly and told me to stop the prednisone. I thought about trying to taper even at that level, but in the end I just stopped it. I did have all of the side effects, but it was bearable. It took me about a year after stopping to feel more or less back to my old self.

Now I've been off of all treatment for a year and a half. My counts are usually over 30 and sometimes over 100. Once or twice they've been in the 20's and I've had to talk my hemotologist into letting me wait and see. After a week they've been safe so it hasn't been an issue. I am very greatful that I have had this remission and have been able to do without treatment.

Lili

Lauren:

Sorry to hear about that reaction. I think it's best to stay away from Rituxan. Your body obviously doesn't like it and pushing it could be a recipe for disaster. It's not worth it. Recent studies have shown that two infusions usually accomplish the same thing that four do, so if it's going to work, you have had enough already. As I said before, sometimes pre-meds do not prevent all reactions. For most people yes but not everyone, especially those who are very sensitive. Getting every single drop of all four infusions is not worth the risk of death.

You do still have other options. You'll find something.

Hi Lauren,

My daughter also had serum sickness due to Rituxan. But, her platelet count normalized after 2 infusions, which is all she had. I wish you the same success. At the PDSA conference in July 2013, I asked Dr. Bussel, one of the medical advisers to PDSA, about an alternative to Rituxan. He mentioned OFATUMUMAB (brand name Arzerra), a fully human monoclonal antibody against CD20. Serum sickness to Rituxan is a result of your immune system reacting to the mouse protein in Rituxan. Since OFATUMUMAB is fully human, the chances of serum sickness are reduced. Thus, Dr. Bussel's recommendation to use OFATUMUMAB. You may want to ask your hemo about it and contact Dr. Bussel as well. His contact info. is available through PDSA.

The chances of serum sickness are reduced with human monoclonal antibodies, but do still exist. My Rheumatologist kept pushing Benlysta which is a human monoclonal antibody, then I read a report about serum sickness caused by that. When I saw her next, she'd heard about it too and dropped the Benlysta idea.

This was written about Arzerra:

"There was no reported correlation between the development of these human antichimeric antibodies and safety or efficacy; nevertheless, the possibility of loss or reduction of efficacy, local reactions, serum sickness/immune complex-mediated disease and major allergic reactions (eg, urticaria, bronchospasm, bronchoconstrictions) is well recognised."

www.clinchem.org/content/45/7/942.full


"A severe infusion reaction resulting in death was reported in a patient with CLL who was given ARZERRA.
- Signs and symptoms of an infusion reaction may include the following: swelling of face or mouth, fever,chills, difficulty breathing, tightness of the chest and/or throat, lightheadedness, nausea, diarrhea, and rash.
- These symptoms can occur during or shortly after the infusion of ARZERRA. If you experience these or any other symptoms, please notify your health care provider immediately.
The prescribing information for ARZERRA is being revised to include new information regarding the potential for fatal infusion reactions.
Patients are reminded that it is important to be closely monitored during and after the infusion by a health care professional, especially if you have a heart condition."

healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2014/40853a-eng.php

"4.3 Contraindications

Hypersensitivity to ofatumumab or to any of the excipients listed in see section 6.1.

4.4 Special warnings and precautions for use

Infusion reactions

Intravenous ofatumumab has been associated with infusion reactions. These reactions may result in temporary interruption or withdrawal of treatment. Pre-medications attenuate infusion reactions but these may still occur, predominantly during the first infusion. Infusion reactions may include, but are not limited to, anaphylactoid events, bronchospasm, cardiac events (e.g. myocardial ischaemia/infarction, bradycardia), chills/rigors, cough, cytokine release syndrome, diarrhoea, dyspnoea, fatigue, flushing, hypertension, hypotension, nausea, pain, pulmonary oedema, pruritus, pyrexia, rash, and urticaria. In rare cases, these reactions may lead to death. Even with pre-medication, severe reactions, including cytokine release syndrome, have been reported following use of ofatumumab. In cases of severe infusion reaction, the infusion of Arzerra must be interrupted immediately and symptomatic treatment instituted (see section 4.2).

Infusion reactions occur more frequently on the first day of infusion and tend to decrease with subsequent infusions. Patients with a history of decreased pulmonary function may be at a greater risk for pulmonary complications from severe reactions and should be monitored closely during infusion of ofatumumab."

www.medicines.org.uk/EMC/medicine/23022/SPC/Arzerra+%28acetate+formulation%29/


This was written about Benlysta:

"Hypersensitivity reactions, including anaphylaxis and death, have been reported in association with BENLYSTA. Delay in the onset of acute hypersensitivity reactions has been observed. Limited data suggest that patients with a history of multiple drug allergies or significant hypersensitivity may be at increased risk."

www.druglib.com/druginfo/benlysta/warnings_precautions/

I have decided to not risk it and just stay away from all of them.

Lauren,
I'm sorry you had such a bad reaction to your last infusion but I'm glad you are alright. That must have been really scary.

I talked to my son about not taking his last 3 infusions. He said since he already has it scheduled for Nov 18th he'll take it and talk to Dr. Bussel then. I know it's silly, but I'm a little nervous because this will be his 13th infusion of Rituxan ; the 9th of this series plus he had 4 doses back in 2006.

Sandi, I was being facetious when I said my son was only on Prednisone continuously for 16 years. I know that's a really long time. Anyway, this was from 1998 to 2004. I dug out his records.[ Boy does that bring back memories. ] The longest he was on daily Prednisone was 4 months. After he got down to 15 mg a day he would go to 20 mg every other day. And to say he was tapered very slowly in an under statement. It took 6 years to taper from 5 mg every other day down to 1 mg then stop it! He got his blood tested every two months or so. If his Hgb went down it stayed the same. If it was good a couple times in a row the Prednisone was decreased.

The alternate day dosing helped prevent the adrenal glands from shutting down. Also he had no physical symptoms i.e. inflammation being treated. Plus he was young, only 7 when he started and young bodies are more resilient. So he had no problems.

Sorry it took me so long to post this. It takes me a while to put my thoughts into words and even longer to put get them in a computer. I have to find a night that I have a couple of hours free to post. In case you don't notice, I learned how to make paragraphs.

Joan

Ha, thanks for the paragraphs.

Okay, so he was on and off of Prednisone over the years and not really on it continuously? That can make a difference. Tapering that slowly also probably helped.

I hope he has a good result from Rituxan after all of that! Keep me posted.