Monday, 31 October 2016

#ClinicSpeak & #NeuroSpeak: alemtuzumab and opportunistic infections

Calling all alemtuzumabers please be extra-vigilant about infections when your lymphocyte counts are low. #ClinicSpeak #NeuroSpeak #MSBlog

I was at a meeting on Friday and heard about a patient who had died of Listeria meningitis after receiving alemtuzumab. Listeria is an opportunistic infection and tends to occur more often in people who are immuno-compromised. Nocardia is another opportunistic infection that has been described post-alemtuzumab (see below). These cases are likely to be at the vanguard and are not 'unexpected'; a case of Listeria meningitis was described in the clinical trial programme and we know from basic principles that immunosuppressive therapies are associated with opportunistic infections. Importantly, you need to know that you can de-risk Listeria to some extent by being on a 'pregnancy diet' post-treatment for the first 3-4 months until your lymphocyte counts have recovered. We recommend that all our patients follow the pregnancy diet for 3 months, which can be found on the NHS Preventing Listeria web-page

Preventing Listeriosis (adapted from the NHS website) 

The best way to prevent getting listeriosis is to always ensure that you follow good basic food hygiene. This includes:

  • Peeling raw vegetables, salads or fruit, or washing them thoroughly before eating.
  • Washing your hands before preparing food, before eating and after going to the toilet.
  • Washing kitchen surfaces and utensils regularly, particularly after preparing raw meat, poultry and eggs.
  • Always separating raw foods from ready-to-eat foods. Don't store raw meat above ready-to-eat foods, because there's a risk that juice containing harmful bacteria may leak from the raw meat.
  • Always cooking food thoroughly and checking cooking instructions carefully, including the cooking time.
For foods that are "ready to eat", the most important ways of reducing the risk of listeriosis are to:
  • not use food after its "use by" date
  • make sure that the temperature of your fridge is 0-5C
  • follow storage instructions on food labels
As an alemtuzumabers' are high-risk group for catching listeriosis, you should avoid eating foods known to be at risk of listeria contamination. Foods to avoid include:
  • soft mould-ripened cheese – such as Brie, Camembert and chèvre (a type of goat's cheese)
  • soft blue-veined cheese – such as Danish blue and gorgonzola 
  • all types of pâté – including vegetable pâté
  • unpasteurised milk
  • undercooked food
It's safe to eat hard blue-veined cheese , such as Stilton, as well as other types of hard cheese, including Cheddar and Parmesan – even if these are made from unpasteurised milk.

Read more about foods to avoid after alemtuzumab and during pregnancy.


Farm animals: Alemtuzumabers should avoid close contact with farm animals that are giving birth or have recently given birth. This is to avoid the small, but serious, risk of an infection.

Read more about the potential risks of close contact with farm animals on GOV.UK.


Please note that alemtuzumab is an induction therapy and is irreversible. Based on its mode of action there will be complications. The only way to de-risk the opportunistic infections is to be vigilant and to take symptoms of infection seriously. If in doubt seek advice. Please note that once your immune systems have reconstituted the risk of opportunistic infections is very low. 


Rau et al. Listeria Meningitis Complicating Alemtuzumab Treatment in Multiple Sclerosis--Report of Two Cases. Int J Mol Sci. 2015 Jun 29;16(7):14669-76.

Alemtuzumab, a humanized monoclonal antibody targeting the surface molecule CD52, leads to a rapid depletion of immune cells in the innate and adaptive immune system. In phase 2 and 3 trials in multiple sclerosis (MS), infections have been reported more frequently inalemtuzumab than in interferon beta treated patients. Here we report two patients treated with alemtuzumab for MS developing Listeriameningitis few days after the first infusion cycle. Both patients recovered completely after prompt diagnosis and adequate treatment. Physicians and patients should be aware of this serious, but treatable complication.

15 comments:

  1. How many cases of Listeria meningitis have there been after alemtuzumab? I am told it is over 20. Will this affect your current position on using alemtuzumab first-line?

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    1. Re: "How many cases of Listeria meningitis have there been after alemtuzumab?"

      I don't know the answer to this question. I am aware of 4 cases; 1 from the trial programme, 2 published cases and the one who has recently died.

      I have written to Genzyme today asking for clarification.

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    2. Re: "Will this affect your current position on using alemtuzumab first-line?"

      No. All our patients are counselled about the risks of treatment and told to be vigilant about infections, including Listeria. As with all rare AEs it will be important to define the overall risk; number of the specific AE over the number of people with MS treated with alemtuzumab. It is also important to stress the risk of opportunistic infections is only really present for a short window when the lymphocyte counts are low. So as with all AEs it is important to get the facts on the table so pwMS considering receiving this therapy can decide whether or not they want to go ahead with the treatment or not.

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    3. ProfG. Do we know how listeria is dealt with as some Lymphocytes are low of years after alemtuzumab?

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    4. I think it is cell mediated immunity so T cells and macrophages

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    5. I did part of my PhD in Marc Feldmann's lab at the Kennedy Institute of Rheumatology. One of the more weathered rheumatologists used to take the Mickey out of us neurologists about being so conservative. He would frequently make the comment that all rheumatologists cause fatalities as a complication of their treatments. The corollary is that if a rheumatologist didn't have fatalities on their books as a result of their treatments that weren't treating their patients aggressively enough. At the time I thought that this rather cavalier approach was wrong, but it is clearly not. Now that we have transformational MS therapies we are seeing serious, and life-threatening, complications. To improve the outcome for the majority of pwMS we are going to have to accept some risk. I think pwMS understand the dilemma and are prepared to sign-up to risks. In fact, pwMS are prepared to take-on much bigger risks than their neurologists.

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    6. Personally I have found the 'heads up' helpful as it's facilicitated my making sure I am yet more informed on hygiene, preventing listeria etc. I'm due to receive Alemtuzumab next week and yes, though the risks are daunting, I am now more confident of playing my own part in off-setting the risks as far as I'm able to. It has also been of benefit to share the post with family and friends so that they don't think I'm being paranoid or excessive and are motivated to show due diligence themselves!

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  2. Does acquiring an opportunistic infection, such as gastroenteritis, shortly after receiving Alemtuzumab alter the effectiveness of the treatment?

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  3. hi, can someone please clarify what is an acceptable lymphocyte count two years after the second treatment. My level is between 0.9 and 1.

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    1. In general aAnything above 0.8 (or 800) is okay; i.e. a grade 1 lymphopaenia.

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  4. I saw a colleague and friend last night who had also heard that there have been over 20 cases of Listeria meningitis post-alemtuzumab. As a result they are starting the pregnancy diet 4 weeks before they are treating patients with alemtuzumab and they are discussing starting antibiotic prophylaxis to prevent this complication.

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    1. I have just had an exchange with a senior Genzyme representative and they have confirmed that there have not been 20 cases of Listeria meningitis. At present they are not in position to release numbers because most reports of listeria meningitis, and listeriosis (systemic disease), are still unconfirmed. In addition, their follow-up of these cases is incomplete and that their database includes duplicate reports. Except for the one fatality mentioned above all the listeria cases have responded to treatment and have done well. It was also pointed out to me that the nocardia case, although fulminant, also recovered. Genzyme stressed that there is no evidence to support starting the 'pregnancy diet' 4 weeks prior to treatment being effective in preventing listeriosis, nor is there evidence to support antibiotic prophylaxis as way to prevent listeriosis. The lack of evidence, however, does not necessarily mean that these two interventions won't work, but Genzyme as a company can't make any recommendations that are not evidence-based. Genzyme have stated that at present there is no new evidence that would lead to a change in their label.

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  5. One might thus presume if a patient has had meningitis than alemtuzumab no longer becomes a treatment option?

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  6. So this Nocardia how often does it occur as a skin n infection rather than in the lungs?

    I've done a bit of reading and found that nocardia infection is often misdiagnosed as a staph infection which, funnily enough, I've been diagnosed with at the GP only last week....hello paranoia cha cha cha

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