Houston we have a problem


Barts-MS rose-tinted-odometer: ★

I did a post a few weeks ago about the secondary malignancy risk associated with longterm continuous immunosuppression and included a survey. The following are the results of the survey, which are quite disturbing. It is clear that a significant number of readers of this blog, although aware of the secondary cancer risk, are not been given standardised information about cancer risk and cancer screening. This is another piece of work that needs to be done and done well. Some of the comments are quite telling as well, including some personal critcism. 

Who is interested in working on an evidence-based calculator of secondary malignancy risk in relation to MS DMTs? It will at least need to include the following variables:

  1. Gender
  2. Ethnicity
  3. Age
  4. Family history
  5. Environmental risk factors, e.g. sun exposure, HPV vaccination status
  6. Type of immunosuppression, i.e. continuous (anti-CD20, S1P modulators) vs. short-term (alemtuzumab, cladribine)
  7. Intensity of immunosuppression
  8. Duration of immunosuppression
  9. Prior treatment history
  10. Prior cancer history

I suspect many health and life insurance companies have actuarial data on this already and could potentially create a risk calculator using real-life data. 

Would you use such a calculator? Comments please. 

CoI: multiple

Twitter: @gavinGiovannoni                                              Medium: @gavin_24211

About the author

Prof G

Professor of Neurology, Barts & The London. MS & Preventive Neurology thinker, blogger, runner, vegetable gardener, husband, father, cook and wine & food lover.


Leave a Reply to Susan B Cancel reply

  • I have had 4 rounds of Ocrelizumab and did not know I had an enhanced risk of cancer. I would be very interested in taking part and/or reading this research.

    • I would absolutely use such a calculator. After going many years with undiagnosed symptoms and little interest or help from doctors, I take a very active interest in my health and like to feel aware of/in control of my body as much as possible. I’d also be interested in participating in any research studies.

  • Would I use such a calculator? Probably not. But general awareness of the risks is a useful reminder to do as much as possible in terms of lifestyle to maintain good metabolic and general health.

  • I have been thinking about this question a lot, ever since I received CNS Lymphoma stats from a very kind anonymous source.
    Now say you CNS Lymph risk is [1%] in year 1 of Natalizumab. Are you hopping to measure whether the risk increases linearly year after year or exponentially (very useful info).
    Are you hopping to measure absolute risk or CNS Lymph risk on natal vs [thyroid cancer risk ] on alemtuzumab, by way of example? (much less useful in my opinion, as your modelling will be exceptionally challenging to isolate non-confounding factors).
    And most importantly, how to treat the outcome? does scenario 1 above give us another tool as to when shift treatments (as was the case earlier on where patients stayed on natalizumab for 2 years in the absence of JCV modelling)?
    Or does it benchmark treatments against each other per scenario 2? (way, way more complicated stuff).

    • I think the 1% risk you quote is too high. There are 25 cases in the EU database but as always we don’t know the numerator. I will ask Biogen for data on this to see if we can get a rate similar to what we have with PML.

      • Sorry G, this was just an example. I thought those marks [ ] indicated so. I should have been clearer, as always.
        The shape of the curve is key here. You would not need to carve out exogenous environmental variables if you were simply doing a like-for-like time series analysis.
        I am convinced that this is the way to go and would definitely start with that personally if I were on your team.

  • As a numerate modeller I would like to see the outcome of such a tool to add to the information available to assist in the choice of treatment allied by NICE. I am supportive of the use of DMTs, but feel the risks appear to be under played. As a pwMS I should be given the information to make an informed choice. There appear to be radical and conservative neurologists and pwMS either follow their favourite or attempt to take a rational look at the evidence. Would this be a question the MS Register could help with?

  • Tentatively sticks head above parapet. Me. I would be interested in working on an evidence-based calculator of secondary malignancy risk in relation to MS DMTs.

    If it helps, here are my variables; I’m a 40 year old, white British female on Ocrelizumab, completed third cycle days ago. No history of cancer, not aware of family history, diagnosed with RRMS 12-13 years ago. Feel free to get in touch.

  • Very interested in this. I have had 4 rounds of ocrelizumab and have never been told about an increased risk of cancer. Would be interested in taking part in and reading any research.

    • We are not sure if ocrelizumab is associated with a secondary malignancy risk based on 7+ years of follow-up. However, based on basic immunological principles in relation to the role of B cells as antigen-presenting cells in peripheral tumour immunosurveillance, I would not be surprised if there is an increased risk, but based on the current data this is likely to be a small risk. The following is what is in the current SmPC:


      An increased number of malignancies (including breast cancers) have been observed in clinical trials in patients treated with ocrelizumab, compared to control groups. However, the incidence was within the background rate expected for an MS population. Individual benefit-risk should be considered in patients with known risk factors for malignancies and in patients who are being actively monitored for recurrence of malignancy. Patients with known active malignancy should not be treated with Ocrevus (see section 4.3). Patients should follow standard breast cancer screening per local guidelines. Please see section 4.2 for populations not studied.

      In the controlled period of the clinical trials, the incidence of non-melanoma skin cancers was low and there was no imbalance between treatment groups. An increase in incidence was observed between years 3 and 4 of treatment due to basal cell carcinoma, which was not observed in subsequent years. The incidence remains within the background rate expected for an MS population.

  • This is definitely something that is not consistently explained by neurologists. Such a tool is a good idea and will aid in decision making.
    Thank you for always pushing forward for MS patients. Hope your recovery is going well.

  • Stephen Reddel at Sydney Neurology in Australia used to have an online immunosuppression cancer screening calculator but they seem to be updating their website and a lot of links are broken.


    “Who is interested in working on an evidence-based calculator…?”

    NO! I’ve lost count of the number of MS tube maps, MS decision trees, MS toolkits, MS risk calculators…… We keep hearing that NHS doctors are overloaded, so I assume you are coming up with these ideas in the middle of the night (bad sleep hygiene).

    Such a calculator will add more confusion and fear to a group of patients who are already confused and fearful. I think there are 15+ MS therapies available (mainly for RRMS). A newly diagnosed patient needs a clear steer by their neuro on what therapy is best for them. When I mean best, I mean a therapy that gives them the best chance of pushing out the time when disability accrues and the time they need to start using a cane, wheelchair…. Neuros should be drawing on their experience of the pool of patients they cover to recommend the treatment which will give their patient the best chances of reducing / delaying the loss of brain cells / spinal cord cells. Throwing cancer risk into the equation is another spanner in the works… it may well steer some patients away from the more effective treatments or from any treatment.

    We also need to acknowledge that cancer treatments are light years ahead of MS treatments. I’d take my chances knowing that an oncologist will have a better chance of stopping cancer in its tracks than a neurologist has of stopping MS in its tracks. We are all going to die and (from family experience) I’d rather go out with cancer than advanced MS.

    We need less fancy graphics and toolkits, and more focus on getting therapies available which address EBV and smouldering MS. We will soon be a quarter of the way through 2021 and I can’t recall seeing one positive MS trial or a breakthrough piece of MS research. My suggestion to Prof G:

    – sort out your sleep issue (the Devil finds work for idle hands to do).
    – no more Covid 19 posts.
    – get a Cockerpoo (I know you lost your dog last year and a new dog will give you an excuse to get out in the park more).
    – a refocus on what patients really need – it’s to know that there is a chance in the near future that progression / smouldering MS can be stopped. Graphics and toolkits won’t deliver this.

    • I was just thinking the yesterday that Sid had been fairly inactive on this blog of late, which is probably a measure of the lack of posts about MS the diversion to Covid, the state of the NHS and society in general. Is this because nothing is happening in MS land? come on Prof, we’ve been stuck inside for 10 weeks. Cheer us all up. I watched yours and MDs informal webinar on HSCT the other day from 2019. It was great. Whatever happened to those? 🙂

    • “We also need to acknowledge that cancer treatments are light years ahead of MS treatments.”

      Somewhat ironic then that many of the MS treatments are in fact repurposed cancer treatments.

      • I might also add that rheumatology is probably streets ahead of us as well and cancer therapies lead the pack.

        The drugs that we use currently in multiple sclerosis are absolutely repurposed.

    • I’m pleased to see from Prof G’s Twitter account that he is “speaking at the Johns Hopkins Neurology Grand Round this afternoon/evening. I am talking about smouldering MS and going beyond NEDA.”

      COVID-19 has really put a dent in MS research over the last year or so. I hope Prof G will share his slides. I, like many on the blog, also think that smouldering MS is the real MS. We can’t just let this hypothesis / observation drift on and on, but it needs to be tested with plausible therapies and ASAP.

      “When Gavin of Johannesburg was 57, he cried salt tears because there were no more MS hypotheses to test.”

      Work smartly Prof G and you’ll be on the next New Years Honours list: KCB – Gavin Anthony Michael Giovannoni. For services to Neurology and Neurological Research.

  • there is no question that MORE info is needed to understand the true impact of what the meds do or do not do as far as upping the cancer risk is concerned. The # 1 reason why these #s will always be obscured is because drug companies that typically collect post-marketing data including INDIVIDUAL patient data points, are typically absent from the ‘crime scene’ if you will. Unless something obvious happens and then a drug like Daclizumab is withdrawn and they cannot hide, the general tendency is to hide the data. There are no data points that I know of, wherein you can surf for information in the post-marketing world of each drug. That is a concern and we can publish material in journals but the information is generally incomplete and obscure. My two cents.

  • I think such a tool would be an excellent resource for those of us who wish to make an informed choice re dmts, although does it assume that we have much control/ choice in this regard in the first instance? which is not really the case in reality 🙈.
    Also, from reading this blog I’m so mindful of the need to intervene early in disease course, and with highly effective drugs, often this is when ppl are not experiencing significant symptoms, and i personally know many who decline drugs for this reason, thinking it won’t be them who progress, I do wonder if this tool would make those very risk averse ppl more afraid of the disease they might get as opposed to the one they actually have 🤔

  • I would be very interested in this information. I was always advised that there was a slightly higher risk of developing cervical cancer with Alemtuzumab treatment. Hence the need for annual smear tests. Having had three rounds of it and no smear test last year due to Covid I would like to know if I should be pushing for one?

  • Hi Prof G, I’m glad you’ve raised this post, as I can vouch for most patients I’m sure, that the information around the side effects and long term use of the drugs, aren’t really discussed in full. I’m guessing as most of us would run out of the consultation, saying ‘no thanks!’ Of course, I’m aware there are risks with any drugs that suppress your immune system. It is just a conversation we should be having with our MS team – not whilst you’re in the midst of invasive tests to see if you have cancer or linking the symptoms since infusion that you’re experiencing be the result of cancer – as this is extremely frightening for all concerned. If you knew more about the drugs (other than a glossy booklet with offering all the support in the world- but certainly not available in the real world!) – you could have conversations with your medical team to be screened and cared for as part of a multi-disciplinary set up! Thus, all HCPs aware of what medication you are on, how it can affect your body and potentially give you the necessary moral support, that gets you through tests and procedures. The scariest thing for most folk – will be having to endure lots of invasive tests for cancer checks, in particular for cervical cancer. Then waiting of possibly up to 2/3 weeks for results, puts a huge strain on you personally and your loved ones.

    I’m thinking – that as a result of being introduced to a DMT (or changing) you should be given regular appointments to ask the questions and discuss any side effects, new symptoms and one the most important things to ask – is ‘how are you and your MS?’ When you have this appointment, your bloods are taken and the reasons and results are discussed properly – so you’re aware if you’re on the edge of too many cells depleting and what the plan should be if this stays low etc. You could also have blood tests to see if you’re showing signs of infection/disease and your vitamin d and b levels, along with thyroid too. Your urine, blood pressure and general reminder and discussion about what medications you’re on – how you’re responding and do you need to change to a better set of meds! All your up to date vaccines can be registered too – to ensure that you’ve had the HPV, Flu, Covid and any others that will help you through life with MS. It would also – be a good time to then support you if there are problems with cancer and if anything is caught earlier enough – you can feel some relief that there might be time to eradicated it.

    Cancer checks could and should be mandatory for anyone who has links with cancer, especially for breast cancer. If you can be referred to gene therapy and be given support early enough – that is what preserving life is all about and moving forward how we should be checking/testing more. The invasive nature of some of the tests, in order to be clear if there’s any abnormality showing in the first-line, can cause your MS to flare and the other healthcare professionals when you are in their care – (say Urology or Gynaecology) communicate and support you and work together. The risk is a risk and although we understand as such, everyone reacts differently and due to the connections, age and other factors – all this should be understood and dealt with by an MS team – not your GP, GP Nurse, MS Nurse, IV Nurse, Urology team, Gynae team! All who are fabulous I have to say – but very rarely, more so at the moment, do make an effort to engage with each other and keep you in the loop.

    I hope all well and I very much would like to see more information about the cancer risks and how the medical world are going to move forward to help patients, who have to deal with another devastating diagnosis too!

    Kind regards

  • Would be interested in the data. I’ve been on tecfidera and want to switch to ocrevus because of cognitive function changes.

  • When my MS was very active and causing lots of damage, I just wanted to start on Tysabri – I didn’t care about PML risk, and I wouldn’t have cared about slightly increased risk of cancer down the line either. When one is is trouble right now, such things are relegated to the ‘cross that bridge when we come to it’ category. And rightly so, I think. Up to a point, anyway.

    • Sorry if I am being too nosey – you mentioned your ms being very active in the past tense, did it calm down when you started Tysabri? Are you still on it and doing ok?

      • Thank you for asking. I am happy to report that I have been on Tysabri for 10 years with no relapses and that I am feeling strong and well, fingers crossed.

        • I should add for completelness that the damage already done pre-Tysabri was done. But the calm and good health that Tysabri has given me mean that I have been able to make the most of everything that does still work. If you have highly active RRMS, and you have a chance to start a highly effective DMD before MS has a chance to take irreversable lumps out of you, please take that chance! I just wish I had had the opportunity sooner.

          • Thanks for your insight

            ProfK is about to start a study ATTCAK MS, where people will be offered the chance of natalizumab at onset, whilst the diagnostic work up and your treatment plan is work out.

          • the attack ms is well needed the irreversible damage i received in the 8 months after being hospitalized and waiting to start tysabri has changed my life considerably!

  • As a cancer survivor and pwms, obviously any increased cancer signal from a DMT is concerning. However, my aggressive MS is also concerning, so on the risk/reward scale my choice was to address my MS first, while the small yet somewhat increased cancer risk is secondary. I am very diligent about regular cancers screenings given my increased risk factors.

    I think DMT mode of action, possible drug failure, developing a DMT contingency plan (i.e. what drug to take next), and monitoring and acceptance of unexpected side effects should be the focus of neuro discussions.

    In my experience, Neuros provide guidance but it is ultimately up the the patient to do the research, educate themselves about the risk/rewards of each DMT, and come to decision they can feel comfortable about. Unfortunately, pwms have to become their own patient advocate.

    • I agree. But it’s a really grown-up decision – isn’t it? – and not all the folks making life-changing decisions about DMDs are grown-up yet, or not very. I’m afraid that the MS specialist’s lot – not an ‘appy one at the best of times – has just got more complicated. Or is about to.

  • I am aware but do not particularly care. MS wrecks my body now, cancer perhaps later.

    I go as far as thinking HSCT has a pretty decent risk-reward trade off (I am usually extremely risk averse, BTW).

    • Totally agree. I Went immediately for hsct and I too am usually a very risk averse person. I could not weigh it up any other way

  • AS a person that has MS I totally disagree that this tool would add confusion. I have used several of the tools and decision making trees crated by BARTS and have found them very helpful. I believe a calculator like this would be great and help to patient and DRs to make informed decisions.

By Prof G



Recent Posts

Recent Comments