Cladribine and the risk of cancer in people with MS

No evidence for higher risk of cancer in patients with multiple sclerosis taking cladribine. Pakpoor J, Disanto G, Altmann DR, Pavitt S, Turner BP, Marta M, Juliusson G, Baker D, Chataway J, and Schmierer K. Neurol Neuroimmunol Neuroinflamm 2015;2:e158; doi: 10.1212/NXI.0000000000000158

You were asking for more official information, and now the wait is over as our study on the risk of cancer in people with MS taking Cladribine has been published.

Inspired by discussions at BartsMS, and executed with colleagues from Oxford, UCL, The London School of Hygiene and Tropical Medicine, Leeds and Lund (Sweden) Universities our analysis shows there is no evidence for an increased risk of cancer when Cladribine is being used as an induction treatment for people with MS.

Cladribine has been on the “BartsMS essential off-label DMT list” (see left upper corner) for quite some time, however having a license only for people with hairy cell leukaemia, but not MS, will always limit its use to exceptional treatment situations, certainly in countries with a high-cost system of health care and regulation.

We believe our work is a key step to put Cladribine back in the hunt for a license to treat MSers. Rather than falling in line with editorials around the globe that kept repeating the EMA’s claim of an increased risk of cancer (the type of mud that really sticks!) we took the published evidence to task comparing the risk of cancer in the CLARITY and ORACLE MS phase III trials of Cladridine with your household brand of DMTs in MS.

We looked at the trials that underpinned the licencing of other current DMTs and found that what was unusual in the CLARITY trial was not the finding of three cancers in the Cladribine-treated group, but that there was ‘no cancer’ in the placebo arm.

Can we say there is no cancer risk with Cladribine? No, we cannot. However, the way to find this out is to monitor people taking the drug long term; a 2 year trial is too short to really get an answer. Obviously, this statement not only applies to Cladribine but all DMTs for MS.

This week has seen the announcement of the potential of B cell depletion in people with relapsing as well as progressive MS.  Rest assured this will be one of the biggest talking points at ECTRIMS next week.  In the wake of the Ocrelizumab success it is of interest to note a key effect of Cladribine is to deplete B cells whilst its effect on T cells is rather modest.  And unlike most other DMTs (including monoclonal antibodies), Cladribine penetrates into the CNS, the key immunological “battle ground” in people with MS.

CoI:  None relevant. This work was undertaken by BartsMS and received no specific funding. We are grateful to Barts Charity for supporting open access.

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    • I'm one for a laugh….but what are you thinking is relevant?

      ProfG was the lead author of the CLARITY study abut is not an author of this work.

    • Laugh as loud as you can. And then simply take the data, and reanalyse them. The studies we included are all out there, no secret filing cabinet with unique tissue sections or the likes.

    • I'm going to analyse them as this analysis is flawed. No accounting for different patient characteristics and methodologies in trials. The best control is that of the placebo group in the CLARITY study.

    • Dr K and MD, Anon 9:37 has a point.
      Even if Prof G isn't one of the authors, it is relevant that so many of the authors are from his team. He is your boss, isn't he?

      That aside, this is excellent news.Keeping my fingers crossed

    • Anon 9:30 Be our guest. We look forward to your analysis, please send us the link once your analysis is peer-reviewed and published. The data is out there and you can do it just like we did in more than one way. Are you going to repeat the meta analysis of the week…..every week?

      Dan Altman is one of the World's most recognised statisticians. However I warn you getting into a debate with a statistician is worse than watching treacle set:-), but maybe you work for the FDA, EMA:-(

      We are talking 0 verses 3 cancers (in twice as many patients). A 2 year study is not the way to assess cancer risk. This could have best been done with a registry and long term follow-up. The oracle trial did not support your view and likewise I suspect that the follow up data of real life in Australia and Russia will support this. Why would Merck Serono be thinking of bringing back Movectro if they thought it was unduly dangerous.

      Will it help Merck Serono going back to EMA? Sure it will independent verification of what they know, They have seen the data it has been presented at meetings. However we are not on the receiving end. We had considered whether they would help out on the cost of publication (£2,500 for Neurology N2..yet publication is expensive), but to keep our independence we had to find this elsewhere.

      Anon 10.25. We said "none relevant". Yes we work with ProfG but this is irrelevant to us, we do not see any consultancy and are not going to be making money if Movecro comes back. For that matter I suspect neither is ProfG.

      The obvious conflict would be if Merck Serono had put us up to this. They didn't. Merck Serono had no input or control in doing this or had no involvement of why we did this. Cladribine is in on our list of Barts Off label drugs.

      This is an option for people with Gadolinium enhancing people PPMS when the trusts won't pay for rituximab. I have seen the cost of generic claribine as little as $32 for 10mg and about £110 for the branded generic in USA. In the UK it is £165 and you need about 50mg a year, so $320 verses $50,000 for beta interferon for a treatment that is much less effective.

      DrK is German and so is Merck is this a conflict too? Where do you stop?

    • MD- from the paper: D. Baker has a patent filed concerning the treatment of multiple sclerosis with cladribine and other compound

    • Yeah and in the context of this paper it is not relevant…..not yet at least, just like being a consultant to companies has no relevance to this paper or being on an editiorial board of a journal is not relevant but they get disclosed.

  • Regardless of the possibility of Cladribine or not cause cancer (nearly all current drugs for treating MS have considerable side effects) I found this excellent news. It's an effective alternative traramento for MS and this makes me very happy, even if it is not something "that will already be immediately adopted" demonstrates the real commitment of BartsMS team has for the issues concerning the disease. … Good news these days, I hope and am hoping to come many more. I am an optimistic person…o//

  • I trust Merck Serono will be showing their gratitude? I suspect the reason they are now reactivating Cladribine is directly down to you guys.

  • Unfortunately, many things cause cancer including life. Age is one of the best predictors of developing cancer; the older you get the greater the chances of you developing a malignancy. Even height is associated with cancer. The latter is probably due to growth hormone driving cells to divide. MSers need to get used to fact that if DMTs keep them alive longer their risk of cancer will increase. It may have nothing to do with the DMT, but simply them living longer. It sounds like the trolls have it in for Team G. You can never win so just keep doing what you do.

    • "It sounds like the trolls have it in for Team G. You can never win so just keep doing what you do."
      Thanks! Don't worry, it's water off a ducks back We're very proud of our work at team G and will never stop trying to make things better for pwMS and if that's a crime, then guilty as charged.

  • Would there be any reason to believe the cancer risk – or lack thereof – with Ocrelizumab would be any different to that of Cladribine?

    • I doubt it would be that much different, but we will have to see what happens when the data is announced next week. I think in the press release they said there incidence of adverse events were similar to placebo

  • If Cladribine needs to be taken more often than Ocrelizumab (which requires an infusion only every 6 months?), and it has more side effects, I personally hope that it will not be pushed as a cheapo option. PPMS (or any kind of MS) deserves the best drugs, because it is a life changing, eroding, destroying disease that, in its milder forms / stages, you have to go around explaining to every —-.

    • The course is taken once a year for only two years for 50% NEDA verses once every 6 months (maybe for life). Not sure about side effects of ocrelizumab (in arthritis lupus studies) but death by infection is not a good one. However there are issues with cladribine and and drug and yes cladribine does a bit more than ocreluzimab, such T cell depletion, disappears for the sys tem within 24h and also easily entering the CNS.

      More convenient, safer, CNS penetrant, more efficacious and potentially cheaper. How will it shape up to Ocrelizumab I don't know but I suspect you will need a cocktail of treatments to deal with PPMS effectively

    • As a person with PPMS, I feel worsenings with viral infections. Get my immune system (B cells) under some control, and I think the biggest problem is sorted. The slow neurodegeneration that neuroprotectives would maybe help really is slow. I hope we're not made to wait for a cocktail if there is something there that can help already. Even if I can't have a whole "normal" life, I'd rather have 10 more good years than nothing. Ocrelizumab has been shown to help, or so it would seem so far. Cladribine has not, yet. So I don't see much point in going on about Cladribine at this point.

    • We will see if the "B cell" immune system is the biggest problem for PPMS results next week. I still think we need neuroprotection as well because there have been so many immune system failures including rituximab in PPMS.

      However if you are right we could be off to the dole office next week if it is a wonder drug. Let's hope it is wonderful news.

      OK. so you don't want me to mention cladribine anymore:-(

      Will we be shot if we take a picture of the result and post it….Someone will do it on twitter. PPMS next saturday. RRMS thursday friday…I haven't looked at the programme. However people were gobbling down biotin on news of the press release and it was a damp squib when the data arrived and only 10% of people were responding.

      Anyway hoping today's post gets me and DrK a free pass into the Merck Serono VIP lounge for some nice coffee and cakes at ECTRIMS, then I can be conflicted:-)

    • I certainly don't want you to lose your job, or lose out on coffee and cakes, come to that! :o) Just don't start shooting down any proven "B cell therapy" for PPMS on the grounds that neuroprotection would be helpful in addition to that. People with PPMS have suffered far too much from the "well, it won't cure it, so you don't get it" attitude. Just something that is proven to help a little would be a huge and wonderful thing. Maybe many – be they researchers, neurologists, politicians, or whatever – fail to see what would be good about a person like me just retaining their ability to draw – or their continence – for 5 more years of their time on Earth. But, by Jove, I do.

  • Is there an increased risk of cancer for Patients with MS regardless of treatment. I've not seen many papers posted on this subject. It would help to know.

  • What about the risk of infertility caused by Cladribine and its possible teratogenic effect? I do not want to spoil the party but for people between 20 and 40. It seems to be an important thing to include that the cost/benefit analysis.

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