Recommended information for prescribers of alemtuzumab

• The SPC for alemtuzumab
• Patient information from the EMA
• Risk management from the EMA
• Advice from the MS Society
• April 2019 EMA restriction on prescribing.

National guidelines for prescribing MS disease-modiying therapies

• NHS England algorithm for MS DMT

Alemtuzumab and Listeria

Guidance on the prevention of Listeria infection after alemtuzumab treatment of multiple
sclerosis from the Association of British Neurology is:

1. The risk of Listeria meningitis/septicaemia is 0.25% in the first month after each
cycle of alemtuzumab treatment.
2. We recommend two preventative approaches, of which the most straightforward
is co-trimoxazole 960mng three times a week for one month after each cycle of
alemtuzumab (that is, following the same schedule as acyclovir).
3. For patients who will definitely be compliant with the Listeria-free diet an
alternative is: eight days of amoxicillin 1g tds or co-trimoxazole 960mg bd to
eliminate Listeria colonisation (starting four days before alemtuzumab treatment)
followed by the Listeria-free diet for one month after alemtuzumab.

For more detail:

• Advice from the Association of British Neurologists on Listeria prophylaxis

Alemtuzumab and blood transfusion: irradiation not needed

In many countries, people who have received alemtuzumab are told that if they ever need a blood transfusion in the future, the blood should be irradiated. The rationale for this is that blood transfusions may contain a small number of white cells (immune cells) from donors. When people with healthy immune systems receive a blood transfusion, these few donor white cells are soon recognised and killed by the recipient’s immune system. But, if the recipient has a very compromised immune system, there is a small chance that the donor white cells will actually attack the recipient’s body (causing “graft versus host disease”). Irradiation of blood stuns any donor white cells and prevents graft versus host disease.

When alemtuzumab was first used in people with leukaemia and lymphoma, this was a real concern, because those diseases and their treatment lead to people having very damaged immune systems.

However, the dose of alemtuzumab used to treat multiple sclerosis is a much smaller and leaves people with healthy immune systems, capable of responding to vaccinations and infections. Therefore, there is no need for people receiving alemtuzumab for multiple sclerosis to have irradiated blood transfusions.

Many countries and regions still work with policies written for alemtuzumab treatment of leukaemia. But I am pleased to say that the latest (draft) guidelines from the British Society of Haematology recommend there is no need for people receiving alemtuzumab for multiple sclerosis to have irradiated blood transfusions.

Unusual side effects of alemtuzumab

“ADEM” neurological deterioration after alemtuzumab, which may respond preferentially to B cell depletion, first reported by Ralf Gold here: Gold B-cell-mediated CNS disease secondary to alemtuzumab…

Haemophagocytic lymphohistiocytosis With colleagues in Finland, we have reported two cases. PubMed PMID: 29602914

ANCA-positive vasculitis. There has been one published, and one unpublished, case. More here.

Sarcoidosis. There have been four cases of sarcoidosis: PubMed PMID: 30307371. PubMed PMID: 30307364.

Arterial stroke and dissection. In November 2018, the FDA identified 13 cases of ischemic and hemorrhagic stroke or arterial dissection that occurred (in 12 of the cases) within 1 day of receiving alemtuzumab. This represents less than 1/1,000 of treated cases. FDA report here. We speculate that this is due to the cytokine surge that occurs with alemtuzumab administration exacerbating pre-existing disease.