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❤

Categories: belimumab, daratumumab, treatment