Case Studies Reveal New Alemtuzumab Side-effects

Research Summary: Severe B-cell-mediated CNS disease secondary to alemtuzumab therapy

A recent report in Lancet Neurology has highlighted two case studies of severe side effects in people with MS receiving alemtuzumab.  The study was primarily a collaboration between Rohr-University Bochum and the University of Oxford.

Alemtuzumab was originally a leukaemia and lymphoma therapy known as Campath, but has since been reassigned for the treatment of multiple sclerosis under the name Lemtrada.  Alemtuzumab is a monoclonal antibody that targets CD52, a protein found on the surface of mature lymphocytes (T and B cells).  The antibody functions to deplete the body of these T and B cells, which works to stop any autoimmune reaction occurring.  It has been linked to a number of side-effects both related to the transfusion process and secondary autoimmune conditions.

In the report, the first individual highlighted was a 41 year old man that had been diagnosed with MS for 11 years.  He had unsuccessfully tried numerous MS therapies across the previous decade before beginning alemtuzumab in July 2015.  Approximately 5 months later, he had significantly worse symptoms and 20 new lesions, most of which were described as “ring-enhancing”.

The second person was a 25 year old woman that had been diagnosed with MS for 4 years.  She had switched between a number of MS medications due to depression and high levels of JCV antibodies.  She began treatment with alemtuzumab in December 2014 and then experienced some severe worsening of symptoms 7, 9 and 11 months later.  An MRI revealed a number of new lesions, including some that fit the same ring-enhancing profile.

In both cases, steroids were used initially to try and stop the attacks.  This was unsuccessful in the man, however, provided some temporary relief in the woman.  In both cases, it was found that plasma exchange (removing affected plasma and replacing it) and rituximab resulted in major improvements.

The success of this strategy to improve the side-effects caused by alemtuzumab treatment indicates that the problems are caused by autoreactive B cells that return after the initial depletion.  Whilst this has been reported previously, these are the first known cases of it occurring in the CNS.  There isn’t enough evidence to determine whether it was a secondary autoimmune condition or a worsening of MS.

These cases should highlight a new problem that may occur after treatment with alemtuzumab in people with MS.  The method for dealing with the side-effects described in this article can be used to help prevent further damage.

The abstract for this study can be read in detail here.