Starting belimumab....

We have a new plan! 

Hi everyone, good to see you back here! 🌺  

I've been absent for some time. Meanwhile, Prof. Wexler has gotten back from his vacation and we've been in touch to discuss how to go forward with the treatment of my autoimmune small fiber neuropathy. I'm happy to report, that we've figured out a new treatment plan, so I guess it's time for an update.

First, how are my symptoms?

Since my break-through neuropathy symptoms returned in mid-August, I haven't been undergoing any drug treatment. I cancelled the planned daratumumab injections. I'll explain why I did that later in this post.

I was quite worried that my symptoms would get really bad without treatment. During my last big symptom exacerbation in summer 2020, symptoms spread and got much worse at a scarily fast pace over a matter of 1-2 weeks. 

Thankfully it didn't happen this time. 🙏🏻 My symptoms have stayed more or less stable over the past 2 months. Maybe they have gotten a tiny bit stronger over time, but much less than I feared. 

My guess is that daratumumab has killed quite a few of my faulty white blood cells, so that my body is currently not able to produce too many auto-antibodies at once. 

I'm not saying I'm doing great. I'm still quite limited in what I can do. But at least symptoms have stayed manageable and I can control my pain levels by avoiding triggers without any additional medication.

So, we need a new plan.....

This is a current picuture of my feet when I have erythromelalgia - this painful red swelling I get in warm temperatures or from walking in shoes. So, neuropahty still prevents me from walking longer distances and obviously from exercising.

Before I started daratumumab, I had to take pregabalin to reduce the burning pain in my feet and legs and I had trouble typing because my lower arms and the bottoms of my hands were painful and hypersensitive to touch. On top of that my nose and my chin were itchy and most clothes felt so scratchy that I couldn't wear them - it kind of felt like sand paper was rubbing against my skin. 

Right now, my feet are sore when I walk, but it's mainly the bottom of my feet that kind of feels like I'm walking on sharp hot gravel. This is annoying enough by itself, however, I can still wear soft flip flops or padded shoes to do small walks without pain. Before daratumumab, wearing any kind of flip flops was really painful, because it felt as though the strap of the flip flops was cutting into the flesh of the back of my feet. 

So far, I'm also still able to type and use my hands quite normally, although I do feel some discomfort occasionally. My nose hasn't gotten itchy (yet) and my legs feel quite scratchy when wearing some clothes (e.g. cannot wear jeans) but most softer clothes are fine and the burning pain has not come back (yet). 

So overall, my symptoms are annoying enough to bother me a fair bit, but they are not nearly as bad as before daratumumab. 

And I have to say, I'd like to keep it this way! 

But enough of my symptoms...

...I actually wanted to update you on my new treatment plan.

Prof. Wexler has gotten back from his 3-week vacation a while ago, and I've discussed my situation with him. In my last post I told you that I'd sent him an audio power-point presentation to summarize all my research on what may have caused my break-through symptoms. When it first happened, we both had no idea how this could happen despite me still undergoing daratumumab treatment. 

I wasn't sure if he was actually going to take the time to watch the 20 minute video. After all, I know that he's extremely busy, and I'm definitely not his only patient and probably also not the sickest one. 

To my surprise he told me that he had actually watched my video twice, and that he thought my hypothesis made sense. 🌺 I didn't expect that, as I was prepared to explain my research to him on the phone. This made me realise again how lucky I am in finding such a good, kind, and open-minded neurologist. Many old-school doctors would probably feel offended and not spend the time listening to their patients' medical hypotheses. At least that's what I hear from many fellow neuropathy suffererers on social media.... 

So why did I get neuropathy symptoms despite daratumumab treatment? 

First of all, I need to state the obvious. Everything I'm writing here is my own hypothesis and has not been scientifically proven. So please, do not take any of this information as proper medical advice.  

I used the month Prof. Wexler was away to do some more literature research, and I also wrote to some experts, who have published cases where they used daratumumab to treat autoimmune diseases before. 

How does daratumumab work? 

Don't worry, I won't go into every detail. And if you don't care about drug mechanisms you can also just skip this bit. 

Daratumumab is a monoclonal antibody, which binds to a glycoprotein called CD38. CD38 is expressed on different cells in our body, but it is most highly expressed on plasma cells. Plasma cells are part of our immune system (part of the B cells, which are lymphocytes/white blood cells) and plasma cells are in charge of producing antibodies. 

Once daratumumab binds to CD38, it causes the plasma cells to go into apoptosis, which means the plasma cells die off. Unfortunately, this is not a specific reaction to plasma cells, which produce faulty autoantibodies. It targets the majority of plasma cells. Therefore, my immune reaction to other infections may also not be as strong as it used to be. But that's the trade off I'm willing to make if it makes my neuropathy go away.

Officially, daratumumab is licensed to treat multiple myeloma, which is nothing else than plasma cell-cancer. In patients with multiple myeloma, cancerous/mutated plasma cells start multiplying too much and obstruct blood flow to other organs. Obviously, that is very simplified and I'm no expert on multiple myeloma at all, but it shows why it makes sense to use dratumumab to treat cancer as well as autoimmune diseases.  

So far so good...

...daratumumab worked really well and within 2 months I was pretty much free from all my neuropathy symptoms.

So the question I wanted to answer with my frantic literature search was:   

Why did I get break-through neuropathy symptoms while using dara? 

I found an interesting study (amongst many others), which looked at plasma cells and myeloma cells of patients with multiple myeloma while they were undergoing daratumumab treatment. 

The authors observed that, as soon as patients received daratumumab, the CD38 glycoprotein pretty much disappeared from the surface of myeloma cells and of non-cancerous plasma cells. They did a lot of research trying to figure out what exactly happens on a molecular basis. I have to admit that some of the molecular details also go beyond my understanding, but what they observed is that after 4-6 months after stopping daratumumab, these CD38 glycoproteins re-expressed on the cell surface. 

The tricky thing is, that in patients with multiple myeloma, this absence of CD38 glycoproteins does not always lead to resistance to daratumumab. It is suspected that daratumumab has some additional anticancer effects which are independent of CD38. A lot of these effects are not really understood yet, as daratumumab has only been on the market for some 6 years. 

Obviously, there are no studies looking at this effect in patients with autoimmune diseases because daratumumab is not an official treatment for autoimmune diseases (yet). However, from my understanding, anticancer effects are not relevant in autoimmune diseases. So in order for dara to work, CD38 needs to be present on plasma cells so that dara can kill them. 🤷🏼‍♀️  

So my best bet as to why I got symptoms while being on dara is that dara had nothing to bind to anymore, because CD38 was not expressed on my plasma cells anymore. The good news is that this CD38 glycoprotein comes back after 4-6 months without dara...so I suggested to Prof. Wexler that we pause dara until winter and he agreed. 

So in summary, I think it might make more sense to....

....apply daratumumab as an interval therapy when targeting autoimmune diseases.

But what do we do until then? 

Wait until my symptoms get worse??? - I'd rather not!

Last year I read a case report of two patients with lupus (another b cell mediated autoimmune disease), who underwent treatment with daratumumab. These patients only received 4 infusions of dara over a period of 4 weeks and then they stopped dara. 

After about 3 months, their auto-antibody titers started rising and symptoms came back. At this point in time they sucessfully started maintenance therapy with belimumab, which stabilised antibody levels and kept symptoms at bay. 

Of course that is only one single case report of patients with a different disease, but to me this made a lot of sense. I suggested to Prof. Wexler that we do the same and start a maintenance therapy with belimumab and see how this goes. If needed, I can then get another 1 or 2 injections of dara some time around January. 

Prof. Wexler agreed, so we have a plan!

What is belimumab??

Belimumab is a monoclonal antibody, which has been licensed for the treatment of lupus for about 10 years in Switzerland. Belimumab binds and inhibits the B-cell activating factor, which is required fo B-cell activation. Thus, belimumab reduces the maturation of B-cells into antibody-producing plasma cells.

If you are interested in the different current and potential future options to treat b-cell mediated autoimmune diseases, this publication may be of interest to you.

We applied for belimumab with my health insurance...

because once again, it's obviously not licensed to treat autoimmune small-fiber neuropathy (like everything else). On top of that it's also not cheap, although it's cheaper than most other drugs I've gotten before (like IVIG, rituximab, or daratumumab). 

Thankfully, they approved our application within less than a week. 🎉 So I'll be starting belimumab therapy soon. You can either get it as an intravenous infusion once a month, for which you have to go into the clinic, or you can do it subcutaneously once a week at home. 

Prof. Wexler discussed my case with the rheumatology department at the hopsital, because belimumab is usually used for patients with lupus, who are treated by rheumatologists. The rheumatologists agreed that our plan was worth a try and they said that doing the subcutaneous injection at home is probably easiest in my case, because I'd have to get my infusions at rheumatology and that would be a whole lot of extra admin. 

Plus I'm happy if I can do my injections at home and don't have to rely on any clinic for that. So I'll do the subcutenous version, and I'll be giving myself an injection with a pre-filled pen once a week. 

Currently, we're in the process of figuring out how, where, and when to do the first injection and whether this needs to happen supervised or not. There is always so much more logistics to everything than I originally anticipate. 🤯

But I'm hoping to start therapy this or next week. Obviously, I'll keep you posted on how things go. I'm always nervous about starting a new drug as you never know how I'm going to react to it. But at least we got things moving!

And on this note, I wish you all a great start into the week. Thanks for following my journey. 💕

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Categories: belimumab, daratumumab, symptoms, treatment