The newest multiple sclerosis drug approved in 2014 was alemtuzumab, trade name Lemtrada. One of the early morning (7:00 AM) presentations I attended at the recent Consortium for MS Centers annual meeting, Independently Supported Symposium (#7): Management of Alemtuzumab Infusions for Patients with Relapsing MS, was sponsored by the drug’s manufacturer, Genzyme, and was for people who work in clinics that administer or plan to give Lemtrada. The presentation was full of facts and an opportunity for me to learn more about the minute details of Lemtrada, since it is still in its infancy of use here in the US.
The talk was given by Christine Cain, MSN, Lori Mayer, MD, and Colleen Miller, MSN, and my article here is a consolidation of their combined comments. The details of the drug, its administration and complications are all factors to be considered by a person before consenting to Lemtrada therapy, and that is the focus of my article here.
What is LEMTRADA ?
Taken from the full prescribing information are these key points :
- “LEMTRADA (alemtuzumab) is a recombinant humanized lgG1 kappa monoclonal antibody”
- “LEMTRADA is produced in mammalian cell (Chinese hamster ovary) suspension culture”
- “The precise mechanism by which alemtuzumab exerts it therapeutic effects in multiple sclerosis is unknown but is presumed to involved binding to CD52, a cell surface antigen present on T and B lyphocyes and on natural killer cells, monocytes, and macrophages.”
- “LEMTRADA depletes circulating T and B lymphocytes after each treatment course.”
Lemtrada is prescribed for patients with Relapsing Remitting MS (RRMS) who have had an inadequate response to two or more other disease modifying therapies (DMT), and ordinarily will not be offered as a first treatment option.
Lemtrada’s use was studied through two large clinical trials, CareMS-1 and CareMS-2. The CareMS-2 cohort was comprised of people who were treatment naïve, meaning they have not been on any other DMT. The two trials combined, gave the researchers the equivalent of 1,622 patient years of Lemtrada use from 811 patients, and much data to review and learn from. From that information a very specific protocol of the administration of Lemtrada was developed as well as a training program for Risk Evaluation and Mitigation Strategy (REMS), that is required for both people who are administering the drug in their clinics as well as the people with RRMS receiving Lemtrada.
How is it given?
Lemtrada is given by IV for five days and then the person is given three more daily doses of the drug one year later, for a total of eight doses. Additional days of Lemtrada may be given annually if there is continued disease activity.
Three days before the Lemtrada therapy begins, it is recommended the person be given high-dose IV solumedrol for three doses. Lemtrada is then given over 5 days – those days do not have to be consecutive for the drug to be effective and could have an interruption in the five days such as the weekend where nothing would be given on Saturday or Sunday. It could also be given every other day, as another example. Because of the monitoring that is required, Lemtrada is usually given as an outpatient, but in certain circumstances the person might be admitted to the hospital.
One year after the initial round of Lemtrada, an additional three doses are given using the same protocol as the five day doses. This may be repeated on an annual basis if breakthrough relapses occur.
The infusion itself takes about four hours at the normal drip rate, but that time may be longer if the person has any sort of negative reaction and the drip must be slowed. After the infusion is complete, there is another two hour monitoring period, before the person is released from the process.
92% of people getting Lemtrada have a reaction during the infusion process and these come from either an allergic reaction or the non-allergic reaction from the release of cytokines. These reactions may become more noticeable and bothersome by days 4 and 5, and can be experienced during or after the infusion. Three percent of the infusion reactions reported may be serious and include: anaphylaxis, bronchospasm, hypotension, hypertension, chest pain, tachycardia including atrial fibrillation, headache, rash, and transient neurologic symptoms. The less serious reactions documented include: nausea, pruritis, chills, insomnia, flushing, fatigue, dyspnea, pulmonary infiltrates, dizziness, and pain among others. A full listing of the side effects can be found at the official site for Sanofi, the parent company of Genzyme.
It is recommended that clinicians be proactive in handling the reactions and anticipate those will occur. They also list a number of opportunistic infections that might occur more easily to people while on Lemtrada therapy. The most serious infections include: herpes viral infections, tuberculosis, fungal infections and listeria.
The person getting Lemtrada must be infection free before beginning therapy and any immunizations such as the influenza (flu) vaccine should be been done no more recently than 6 weeks before the IV infusions begin. AFTER the five days of Lemtrada the person should not have any live immunizations, and has to wait a minimum of 6 months before having any other vaccinations.
Side Effects from Lemtrada
99.9% of people infused with Lemtrada experience lymphopenia, a condition of severely decreased lymphocytes, within one month of the infusions. 40% of people returned to near normal levels in six months, and approximately 80% had near normal levels of lymphocytes at the 12 month post-infusion mark. Lemtrada works by removing the T and B cells in our immune system, and then it is allowed to rebuild itself to normal levels. B Cells begin to return in about three months while the T cells are slower. The depleted lymphocytes is the desired result of the drug.
The immune system is depleted through Lemtrada therapy and makes the recipient more susceptible to other autoimmune disorders, the highest reported being thyroid disorders in 34% of patients. Other autoimmune disorders might include immune thrombocytopenia purpura (ITP – a blood disorder that can be fatal), or anti-glomerular basement membrane disease, which affects the kidneys. There is an increased risk of thyroid, melanoma and blood cancers for people treated with Lemtrada. Patients are monitored regularly for the autoimmune disorders and thyroid cancers. The ITP test is done monthly, and thyroid tests are performed quarterly (every three months).
Results for Lemtrada
The clinical trials were performed comparing Lemtrada against interferon beta-1a (Rebif). In the first study, which included people who had tried other DMTs, at year 2, 65% of the people treated with Lemtrada remained relapse-free, while that number was 47% for the people given interferon b-1A.
For the second study, which included only treatment naïve people – with no prior use of any DMT – these numbers increased for both drugs. At year 2, 78% of the people treated with Lemtrada remained relapse-free, while that number was 59% for the people given interferon b-1A.
It was impossible to attend every session at this meeting, and I found myself torn between topics. Alemtuzumab (Lemtrada) was the discussion of several other presentations and some fine MS specialty news outlets covered those talks in detail. Alemtuzumab May Suppress Disease Activity for Four Years is one such reference and gives greater details on follow-up studies that found people treated with Lemtrada continued to achieve good results after four years of the initial therapy.
At the end of the presentation there were very few questions and even fewer people present who indicated they currently give Lemtrada. The use of this powerful drug is not to be taken lightly and the lengthy list of possible reactions and complications as well as the financial implications are sobering. If you were on Lemtrada during these trials or since it has been approved for use, I’m sure others as well as myself would like to hear about your experiences. Please drop us a note and let us know what it was like and how you are doing now.
Wishing you well,