In late 2016, when Maddi developed a central line infection, it was discovered that her IgG levels were bottoming out each week following plasmapheresis. Her health was at a very crucial point, and she was dangerously close to a scary place where even a small infection could mean live or death. It was then our Team suggested using Bortezomib (Velcade), a chemotherapy drug primarily used in the treatment of multiple mylemoas (cancer), to take the place of plasmapheresis, and hopefully save Maddi’s already fractured immune system. As with every medication, I poured the internet looking for information regarding the use of Bortezomib and Autoimmune Encephalitis. I found very little. In fact, the information I did find was cutting edge, published in December 2017, as it was very new that Bortezomib was suggested in the treatment of Autoimmune Encephalitis. It seems that in theory, the way that Bortezomib works in the body, seems to address the way Autoimmune Encephalitis attacks the body, thus removing the need for more invasive treatments such as plasmapheresis.

I’m not a medical doctor, but I will try and explain the mechanisms, as well as Maddi’s experience so far in the last 6 months of treatment with Bortezomib.

Plasma cells are a very important part of our immune system. Plasma cells, is a short lived antibody producing cell that are derived from B cells. B cells differentiate into plasma cells that produce antibody molecules closely modeled after the receptors of the precursor B cell. This means your ability to fight the common cold, flu, and infection comes from our plasma cells. In Autoimmune Encephalitis, namely Anti-NMDA Receptor Type (Maddi’s type), the plasma cells in her body have produced antibodies that are attacking the Anti-NMDA receptors in her brain. Each plasma cell can secrete several thousand antibodies into circulation. In healthy persons, the antibody production stops when the initial stimulus is removed, such as recovery from an infection or virus. This is not the case for most cases of Autoimmune Encephalitis, with the exception of para-neoplastic AE’s where the initial cause/trigger is a tumor or teratoma. With AE, the body creates these antibodies at an alarming rate, which in turn attack the brain. First line defense is to always use steroids and IVIG to calm the immune system, and to suppress these plasma cells from creating more antibodies. In a lot of cases, this seems to be enough, and patients go on to recovery. In cases like Maddi, first line treatments did not work. This is when we introduced second line treatments such as Rituxan and Plasmapheresis. Rituxan works to stop production of B-cells. On the cellular level, if B-cell production is stopped, then they can’t mature into the plasma cells that are creating the antibodies to attack Maddi’s brain.

So, stop making B-cells, prevent plasma cells from creating antibodies. Thank you Rituxan! Maddi’s B-cells are zero. She’s not making any! The problem with using steroids, IVIG, and Rituxan, is that none of those treatments do anything for the plasma cells that are already mature and producing antibodies. It also does nothing for the antibodies already circulating in her blood, in her bone marrow, and body tissues. This is where plasmapheresis comes into play. Plasmapheresis works by filtering the blood to remove those antbodies. Removing the antibodies that are already circulating in her blood stream help to stop the attack on the brain. Maddi did plasmapheresis for 6 months with much success. She had a dramatic recovery period. I will stand by saying that PLEX brought her back to us, and we had a very uneventful fall, with glimpses of our girl back. So, let’s recap. B cells are not producing antibodies. So nothing should be still attacking her brain. Suppressing the immune system with steroids, and periodic treatment with IVIG. But, Maddi is re-escalating and continuing to have trouble? What’s going on?

It was explained to me that Plasma cells are believed to be short lived, but there is no guaranteed timeline of when that happens. Plasmapheresis filters the blood of antibodies, but does nothing for plasma cells. They are still floating around and wrecking havoc. Plasma cells and antibodies can also pass into body tissue and bone marrow, meaning, although Maddi’s blood titers are zero, she could still have antibodies hiding out. This is where bortezomib (Velcade) comes into play, wiping out plasma cells, and erasing the last link in the chain of antibody production. Our Rhuemotologist told us there was no real ways to measure plasma cells, because they can exist in tissue, so we’ll have to gauge effectiveness on clinical presentation. The point of starting bortezomib to avoid having to continue on steroids or PLEX, long term.

Four her first round, Maddi was given 4 doses of bortezomib over a 5 week period. The dose is given in a subcutaneous shot to minimize side effects. When given through an IV, it can have terrible side effects such as vomiting, nausea, and hair loss. The risk to Maddi for these side effects is very low, when given subcutaneously. We also spaced her doses out far enough to avoid development of peripheral neuropathy. This is the more common side effect, but is alleviate by given small doses, spread over several weeks.

We are about 6 months post her first round of injections, and we recently started her second round, with the same treatment plan. After steroids and PLEX were withdrawn, Maddi had about 8 weeks where she was free of AE symptoms; then middle of April, she began to have flare symptoms again. Her doctors are hopeful that a second and third round will knock the rest of her plasma cells out, and put her into remission. For now, it’s unclear the effectiveness of Bortezomib in treating Maddi’s Autoimmune Encephalitis, but it seems very promising, given how the medication interacts with the disease.  There is research published that supports positive outcomes in patients with Anti-NMDA Receptor Encephalitis. This makes me hopeful very hopeful for remission.

For more information about the use of Bortezomib (Velcade) in the treatment of Anti-NMDA Receptor Encephalitis, please read here:

https://aealliance.org/bortezomib-treatment-for-antinmdar/

http://www.practiceupdate.com/content/bortezomib-for-treatment-of-anti-nmda-receptor-encephalitis/48844

https://www.sciencedaily.com/releases/2017/01/170106130934.htm