Daratumumab restart

Daratumumab here we go again 

Hi everyone, good to see you back here! 🌺

It's been a while since I told you that I'd had a flare of small fiber neuropathy after a viral infection in early December. 

In the first half of January, I got 2 doses of daratumumab to get this flare back under control. In this post, I'll talk about how this has been working so far. 

So lets start where we left off!

My neuropathy flare had calmed down a bit by the end of December... 

but I still had trouble with my feet as well as some other symptoms. In my diary I wrote (it's impossible to remember symptoms otherwise), that the bottom of my hands and my lower arms were sore when typing and that I had to wear sweat bands on my wrist to avoid discomfort. Also my nose was itchy and the tip of my tongue felt as tough I had burned it. 

The burning tongue symptom can occur with small fiber neuropathy. I don't think it's really known how often this occurs. I have recently talked to a friend who has the same thing and who has SFN as well. Apparently she knows quite a few others who have it too. It took me a long time to realise that this symptom correlated with the severity of my neuropathy and, thus, must be related to it. It's not terrible in my case. It just kind of feels as though I had drank a tea the day before without waiting for it to cool down first. 

Over New Year's Steve and I spent 5 days in the mountains 

which was lovely and relaxing. We did go for some walks, and I was surprised that it went better than I had feared. I did some 10'000-step walks in the snow in my Ugg boots. I did notice that my feet would get warm after a while, and whenever I took of my shoes they were a bit red, swollen, and sore, but they would calm down again. However, I could still not wear normal shoes without my feet getting pretty sore. Before my flare up, I had just started wearing other shoes than Ugg boots and had started exercising on my crosstrainer (bare-foot). 

The continued symptom improvement was likely due to belimumab (Benlysta) 

which I've been taking once a week since October. Whenever I had a flare of symptoms before, it would never calm down much on it's own. Doctors would always tell me it might just pass, but over the years I've learned, that this doesn't happen for me. Without some sort of drug treatment, symptoms would always get worse or at least stay the same. So far, belimumab has not been able to prevent the flare due to my viral infection, but at least I could see a steady slight improvement over time. This is a lot actually, because even a slight improvement in symptoms is worth a lot!

Plus, who knows how bad this flare could have been without it?? 

However, belimumab is not a drug that has an immediate strong effect, so its best to combine it with something else and/or to use it as a stabiliser once the neuropathy is more or less under control. Thankfully, I tolerate belimumab well, so it's planned that I keep taking it for the unforeseable future. 

To speed things up, I got 2 doses of daratumumab January 7 and 14

In an earlier post, I wrote about my literature search and that Prof. Wexler and I had decided to go for a maintenance therapy with belimumab and to only use daratumumab in intervals. This is pretty experimental, but given that I had a relapse while on maintenance therapy with daratumumab last summer, this was the best plan we could come up with. 

We decided to do the first infusion as an intravenous (iv) infusion. So I had to sit at the hospital for a whole day with a drip in my arm. Last summer, I got all my daratumumab doses as subcutaneous injections, which is a lot easier to handle. 

Why did we opt for an iv infusion instead of a subcutaneous injection this time?  

Basically, our hypothesis is that most of the reaction to daratumumab (i.e. killing of plasma cells, which produce antibodies) happens very soon after the drug gets into the blood stream. Plasma cells express the highest level of CD38 proteins on their surface before they are exposed to dara, and they start to downregulate them once they get in contact with the drug (this is very simplified). 

Daratumumab binds to CD38 expressed on the surface of plasma cells. So in order to get the most interaction between dara and my plasma cells, we figured we want to make sure that there is a high concentration of daratumumab in the blood stream right at the beginning (i.e. we wanted a high peak concentration). 

With subcutenous injections the compound is injected into the fatty tissue (usually of the belly) and then slowly diffuses into the blood stream over 1-3 days. With an iv infusion, the drug is right there as soon as you let it in. 

There are several benefits of subcutaneous injections, which is why they are generally more popular. Most importantly, they cause less allergic reactions, because the body doesn't have to handle all of the drug at once. But given that I'd never had any adverse reaction to dara so far, we figure this is a risk we can take. Subcutanous injections are also easier to apply because you can inject them within 10 minutes. So they're less work for the hospital staff and less time intense for the patient. However, after the first subcutaneous dose of daratumumab after a treatment free interval you have to sit at the hospital for several hours after the injection anyway to make sure you don't have an allergic reaction. So it didn't make a huge difference in terms of logistics in my case. 

For multiple myeloma, daratumumab is pretty much always given subcutaneously these days. However, there are probably some other/additional mechanisms at play when giving daratumumab to treat multiple myeloma vs autoimmune diseases. I discussed this question with my hematology friend as well, and she confirmed that they give dara iv to patients with autoimmune diseases for this reason as well. So, Prof. Wexler and I decided we might as well do it properly and go for iv. 

So, I spent a day at the hospital and got the infusion over 9 hours 

This sounds worse than it was. I actually had a bed for the day and was able to binge Netflix all day. An hour before the infusion started, I got pre-medicated with steroids and an antihistamine, which made me super tired. So, I was kind of dosy all day watching silly reality TV shows. 

Thankfully, it all went smoothly. I didn't have any adverse reactions and felt fine as I left the hospital. I was also a bit worried to spend the whole day at the hospital, because COVID numbers are very high in Switzerland at the moment. So if you spend a day in a room with some other people, chances that one of them has it are currently pretty high. 

Catching COVID on the day I get immunosuppressants loaded into your blood stream was not exactly what I wanted. But I managed not to catch it (I did have my FFP2 mask on at all times and only took it off to sip on my drink or to have a bite to eat). 🪵🤛🏻

The only thing I noticed is that I must have developed some sort of allergy to bandaids over the past months. After they freed my from the iv drip, my arm looked like this and stayed like this for about 3-4 days. I didn't use to get this last year, but it wasn't itchy or anything, so that's no drama.🙃 

One week later I went in to get my second and currently last dose of daratumumab, which I did get as a subcutaneous injection this time. I had to sit there for 2 hours after the injection to make sure I didn't have an allergic reaction, but then I was good to leave and done with dara for now. 

Did daratumumab work again??

I was quite anxious about this actually, because after all, I did have a neuroapthy relapse while on dara therapy last summer. After reading all the literature, Prof. Wexler, N (my hematology friend), and I agreed that it's likely that dara will work again. But who knows, right? This is all experimental, and things often play out differently in clinical practice than one expects. So you just have to wait and see and hope for the best.

After my first infusion, I was quite nervous about what would happen...

But I noticed quickly, that it was definitely doing something again!

Within a day I could feel that my symptoms increased in intensity. Strangely, the same thing happened when I first started daratumumab in May 2021. Symptoms got worse for about 2 weeks before they started to get better. 

My hypothesis is, that when dara kills plasma cells, it sets free an extra load of autoantibodies, which were trapped in the plasma cells before. I picture this like a little 'plasma-cell-explosion'.💥 This is probably not what's really happening, but it helps me to make some sense of what's going on. 

It's also known that neuropathy symptoms can be perceived as worse when nerves start to heal, because you have more feeling in your nerves again. However, I doubt that nerves would start healing within a matter of a day, because antibodies usually take about 1-2 weeks to clear from the blood stream.

So who knows what's going on....🤯 

But this is the change in symptoms I noticed: 

The day after the infusion, I noticed that I felt as though I had a strange band over my nose. This wan't painful, but it just felt as though someone had put tape over the back of my nose. Over the following 1-2 weeks I also noticed that I developed erythromelalgia (red, hot, sore skin) a lot faster. I said to Steve, it just felt as though my skin was a lot more nervous than usually. 

This is a photo of my legs 3 days after the first infusion after having a moderately warm and not very long shower. The same thing happened to my feet and hands. They kind of felt warmer and more hypersensitive than before the infusion and were a lot quicker to play up and develop erythromelalgia whenever I did any sort of activity. I spare you a photo of my feet, because I really need a pedicure (which I don't dare getting atm due to extremely high COVID numbers) and you've seen plenty of photos of them anyway.😂

About a week in, I also noticed that I was more itchy all over and I had more of these weird muscle twitches (fasciculations) mainly on my legs but also all over my body. Overall, it was pretty similar to what I had experienced during my first round of dara. 

I was very happy to see a clear reaction to dara, so I was more than willing to put up with some increased symptoms for a few weeks. It's weird how you can be happy about symptom aggravation. After all, it's always about hope and future outlook. 

About 10 days after the first infusion I started to notice improvement

The first thing I noticed (like last time), was that my pinkies did not feel weak or clumsy anymore. Losing some strength in my pinkies is always one of the first signs I notice whenever my neuropathy takes a turn for the worse. It's not like they are paralysed or anything, but I just notice that they have less strength than the other fingers. About 10 days into treatment, I put on face cream in the morning and noticed that my pinkies cooperated with me perfectly. 

I was also slowly able to do longer walks in my Ugg boots again without my feet playing up. One day I did a very short walk (5 minutes) in 'normal' (non-padded) shoes, just to see how this goes. I managed without feeling discomfort. After about 5 minutes I did feel some pressure on my left forefoot, but before dara I would feel uncomfortable right away from the first step on. 

I was able to type for a while without dyscomfort on my hands/lower arm. I started doing small rounds of exercise on my cross trainer (15 minutes at the time on a low setting of resistance), which I managed without major hiccups. My toes would still get a bit red, but they would calm down quickly. Before that, a round of exercise would result in a payback of sore feet all evening.

About 3 weeks after the first infusion I put on jeans for the first time in a long time, and it was fine. I have to say, they were soft stretchy jeans, but this was a major achievement for me. I used to always be a jeans and t-shirt kind of person. But ever since my neuropathy got worse in summer 2020, I haven't been able to wear jeans, because the fabric just felt like sand paper rubbing against my skin. But I'll wait a bit longer until I try some proper jeans on. I remember, even last summer, when I was in 'remission' they felt very scratchy when I tried some on.

 

So how am I doing now? 

Once again, it's all about being patient. I'm definitely much better than before daratumumab, and very much better than just after my viral infection in December. But I'm still not symptom-free. Last spring it took about 2 months until symptoms were more or less gone. The weird thing is, that nerve healing comes with a lot of symptoms on its own, and it's so hard to tell apart, which symptoms are symptoms of healing and which are classical neuropathy symptoms. Unfortunately, it's not possible to take a drug and symptoms disappear all at once, because nerves need to heal first and that takes time. 

So far, I have not developed any bad hypersensitivity like last time. My theory is that this may be because my neuropathy was not as bad before the dara infusion this time around, so the nerve damage was not as extensive. Moreover, I was also on pregabalin before starting dara in spring 2021, and then reduced pregabalin gradually, once I started to see improvement. Maybe this could also had something to do with hypersensitivty, so once again, who knows. 🤷🏼‍♀️

Either way, I'll leave it at that and will keep you posted. For now I can say that I'm very happy that our hypothesis has played out and that daratumumab seems to be doing something again. I was worried that I had built up a permanent resistance to dara last summer, and at least this doesn't seem to be the case. I hope that we are one step closer to figuring out a long-term treatment plan for my small fiber neuropathy.🪵🤛🏻

Thank you all for your interest in my journey and all your thoughtful comments and inputs. If you want to be notified of future posts, click below to never miss a post❤

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Belimumab 1-month update

I started Benlysta /belimumab a month ago 

Hi everyone, good to see you back here! 🌺 

I figured it's time for an update, although there's actually not much to report. I guess that's a good thing. The first month with Benlysta (which is the brand name, and belimumab is the active drug compound) has been event-free...

I had my first injection in early October...

I use the subcutaneous Benlysta autoinjectors, which I inject myself with at home once a week. It's suggested that you do the first injection under medical supervision, in case you have an allergic reaction. 

So, for the first injection, I had a nurse, who works for my pharmacy, come to my place to show me how the injections are done and to stay with me for an hour after just in case anything happened. 

It's not like you need much instruction to do these injections. They are super easy. You get these pre-filled pens, which you keep in the fridge. 

Half an hour before the injection you take them out of the fridge. And when you are ready to do the injection, you desinfect the skin and push the pen down at the injection site. Then you hold it down for a few seconds until you hear a clicking sound. 

I was a bit worried that the injections would hurt...

...because I read some online reviews, which said the injections were so painful, that they don't even manage to inject the entire liquid before they have to withdraw the pen. Some people even switched to intravenous infusions for this reason. 

Most people who made this complaint seemed to inject into the upper leg, so I decided to stay away from my legs and aimed for my side flank, where I never had problems doing the subcutaneous immunoglobulin infusions. Basically you can inject into any site of your body, where you have a bit of fat...so that you don't hit a muscle🙃

Thankfully it really didn't hurt much

I can feel a bit of a stingy/burning feeling during the few seconds I do the injection, but it's barely worth mentioning. So in case you ever need Benlysta, don't worry too much and just try it out.

But now to the more important questions:

Has it improved my neuropathy (yet)?

I wrote in my last post, that Benlysta is a slowly acting drug, and that the main purpose of starting it, was to stabilize my neuropathy symptoms at a mild level for now. Benlysta is licensed to treat patients with lupus (another autoimmune disease), and the general notion is that it takes on average 6-9 months until lupus patients see a notable improvement of their symptoms with Benlysta. 

I didn't expect to notice anything right away, but of course, once I start a new treatment, I'm focused on my symptoms to spot any changes, because after all you never know. 

So far, I can report that symptoms have been stable on a rather mild level. My hands are doing mostly fine and I can walk fine in padded shoes and can wear most clothes without discomfort. 

However, I still have trouble walking longer distances in non-padded shoes and my feet get warm and red/sore in very heated rooms or when I excert myself. Mind you, I'm far away from running marathons - so by exertion I mean 15 minutes on my home trainer on a casual setting..... 

Thats my feet after a walk the other day in my Ugg boots. They get a bit red and sore when they get warm, and I have these weird red spots. But after taking off my shoes they cool back down to normal and stop being painful.

About a week after starting Benlysta I started to be more itchy 

I noticed that my hands, feet, lower legs, and my arms would get pretty itchy once in a while, and espcecially after physical activity. This hasn't stopped yet. I still find myself scratching my skin more often than I used to. For me, itch has been a symptom whenever my neuropathy has been improving/healing in the past. I assume this must have something to do with nerve fibers gaining back function or regrowing. 

However, the problem with itchiness is that it can totally also be psychosomatic, so I really don't want to read anything into this. For me, I always get super itchy in my face exactly when I'm carrying a tray full of glasses or something and I know I can't scratch right now. Or I get itchy everytime someone tells me about being itchy....so yeah. 

And on top of that winter has just settled in, and rooms are being heated again, which always makes my skin a bit dry and itchy....So I'll wait and see...I'll keep tracking my symptoms and I won't draw any conclusions before a few months into treatment. 

The plan is to observe what happens for the next two months, and if I still have substantial symptoms in early January, I will get one or two additional shots of Daratumumab, while I maintain my Benlysta therapy. 

Do I have side effects from Benlysta? 

Thankfully, so far I haven't noticed any...🙏🏻

Starting a new drug therapy always comes with quite some anxiety for me. You never know what to expect. And being a pharmacist, of course I get informed before starting a drug. I must say, sometimes it would be easier not to know much about those drugs, but of course I can't help myself anyway...

I'm also quite traumatised from my IVIG infusions (intravenous immunoglobulins), which I had around 2 years ago, and which gave me meningitis (worst headache and nausea for days and weeks on end) after every single infusion. This was super debilitating, and I was not warned about this beforehand. But I will write about that in another post. 

The potential side effects that are reported for Benlysta/belimumab are: 

• a potentially increased risk for infections, as is the case for all immunosuppressants. However, studies have actually found that severe infections happen very rarely. So that's a trade off I'm happy to make if it helps my small-fiber neuropathy. 

• A potentially increased risk for cancer, which is also stated for every immunosuppressant, because the immune sytem helps to fight cancer. However, again studies have not found a relevant cancer risk for Benlysta so far. 

• Headache, nausea, or diarrhea. But these are literally listed for every single drug on the market, so that's not to worry about too much.

• Allergic reactions, which obviously can happen to every drug. But once, you managed the first few injections without a reaction your chances of having one are very slim. 

I was quite worried about allergic reactions, because I'm well aware that my therapy options are narrowing down. Any drug I don't tolerate is one less option to treat my neuropathy. 

So for the first two injections, I decided to take an antihistamine and another allergy drug (montelukast) an hour before the injection, just to be safe. I take these drugs before daratumumab injections, on the advice of my heamatologist, so I figured they can't hurt. But after I never had a reaction, I stopped taking them and it's been fine so far. 

• The one side effect I was/am worried about most is a reportedly increased risk of depression and suicidal ideation. 

The patient and doctor information presents a whole section stating that you need to inform your close ones so that they can look out for any changes in your mood or behaviours....which freaked me out quite a bit. Depression is exactly what you need while fighting a rare and under-studied chronic disease and chronic pain. 🤯  

Is this for real? Will I develop depression now on top of everything??

Being a bit of an OCD-researcher, of course I went and got the original studies where they evaluated Benlysta, to see where this warning came from. And what I found was actually quite reassuring, that my chances of developing depression due to this drug don't seem overwhelmingly high. 

What follows now is a bit scientific, so if you're not interested in this, you may as well stop here. But as an epidemiologist who reads these kind of studies for a job, I think it's really interesting....maybe I'm slightly biased.🙃

In one of the first randomized trials to evaluate belimumab in patients with lupus, they reported that 6-7% of patients in the belimumab group developed depression, compared to only 4% in the placebo group. And a later long-term follow-up study (table below) of these patients, showed, that most of those patients developed depression in the first 2 years after starting belimumab. 

Subsequent studies obviously looked very closely at the risk of depression in patients who are treated with belimumab, and most of them could not reproduce this finding. A study that was published in 2020 (in the best medical journal, table below), which evaluated belimumab to treat lupus patients with active nephritis (kidney inflammation) actually found more patients with depression in the placebo group than in the belimumab group. 

A summary analysis (meta-analysis) of all randomized trials evaluating belimumab did also not find an icreased risk for psychiatric adverse events in association with belimumab when compared to placebo. 

So obvioulsy, the book on whether or not belimumab increases the risk for depression and other psychiatric diseases is not closed yet, and most studies actually find no increased risk. But it remains to be clarified why this one study found an increased risk. It could just be a chance finding, or it could have something to do with the way they collected their data, or whatever..... There have also been case reports of people who credibly report developing depression with Benlysta.

However, the whole topic is complicated by the fact, that belimumab has only ever been studied in patients with lupus, and that lupus itself can cause depression and other psychiatric conditions. So treating lupus, may well have an impact on psychiatric symptoms....all pretty complicated. 🤯 

However, once a warning like this made it into the drug leaflet, it is very difficult to remove it from there. But as a patient, who only reads the warnings without the background info, this is scary. 

It took me a whole day of literature search, to be re-assured and confident enough to start belimumab. Nonetheless, during the first 2 weeks, I was obviously over-analysing my mood for any changes. Very relaxing I know.🙈 

But after a month of treatment, I can report that, I think, my mood is unchanged. KNOCK ON WOOD!🪵🤛🏻 

However, should you ever find that I've become more depressing and/or annoying than usual, then please let me know and we'll just blame it all on Benlysta/belimumab. 😂

And on this note, I wish you all a great week. I hope you were not too bored by this update, as stabilized conditions do not make for exciting stories, but I'll take it! I'll keep you posted on my progress and hope to finally also write down some other posts about other treatments I've had in the past. 

Thank you all for your interest in my journey and your support.💕

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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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