Tuesday, 8 May 2018

Therapeutic doubts - regression of skin cancer after stopping fingolimod

Mult Scler. 2018 May 1:1352458518774444. doi: 10.1177/1352458518774444. [Epub ahead of print]

Spontaneous regression of tumor-stage cutaneous T-cell lymphoma in a multiple sclerosis patient after discontinuing fingolimod.


Froehlich A, Schmidt S, Landsberg J, Bieber T, Wenzel J.




Despite the side effects of MS treatments, I still believe that without them we'd be a lot worse off. The damage done by MS, the visible and not so visible, are such that the risks in a majority are justified. But, I am no stranger to doubt; it comes and goes. A fleeting shadow that slips from the mind, only to resurface with the publication of another adverse event.

Fingolimod, is a relatively safe drug as far as highly active MS drugs go. Around two years ago, a signal with skin cancers (basal cell carcinomas) became apparent. Now Froehlich et al. in a letter to the editor report a second case of cutaneous CD30+ anaplastic large-cell T-cell lymphoma. A case similar to this one was reported back in 2016 by Papathemeli et al. (Development of a primary cutaneous CD30(+) anaplastic large-cell T-cell lymphoma during treatment of multiple sclerosis with fingolimod). In both instances, they have followed initiation of fingolimod and resolved after its discontinuation. I have also blogged on cutaneous lymphomas on fingolimod before: http://multiple-sclerosis-research.blogspot.com/2017/12/blood-cancers-after-fingolimod-treatment.html

The authors point out that such skin cancers are not unusual and seen in organ transplant recipients under long-term immunosuppression. Unlike other MS disease modifying-drugs fingolimod keeps the lymphocytes in the lymph nodes, it is therefore possible that this mode of action prevents tumour controlling T-lymphocytes from reaching the skin where tumor cells are proliferating. The reduction in immune surveillance with fingolimod is likely to throw up other cases in the future, over and above those that simply escape immune surveillance (i.e. in the presence of an apparent normal immune system). On a separate note, the occurrence of secondary malignancies with chronic immunosupression needs to be investigated in greater detail, together with workable strategies on how to overcome them in the near future.

6 comments:

  1. Dear NDG,

    You have to use the tools that you have in your toolbox today. Maybe tomorrow, we’ll find a better tool? Sorry I don’t have a better answer.

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  2. It often seems to me that the MS population is acting as a large group of guinea pigs in an experiment to see just how deleterious might be the effects of long-term immunosuppression.

    Yes, the second-generation MS drugs have proven to be quite effective in reducing relapse rates and enhancing lesions, but at what ultimate cost? My great fear is that over the next 5-10 years we will see a considerable amount of cancers and other unforeseen consequences as the result of profoundly altering the workings of the human immune system. There's a reason we evolved this highly intricate and interconnected system, and the fact of the matter is that the aberrant immune response seen in MS is not the cause of the disease, but rather a symptom of some much deeper ill.

    I'm especially concerned about Ocrevus. In the progressive MS trials more than one in 50 patients developed cancer. This has thus far been discounted as an outlier, but what if it's not? How much damage will be done to the patient population and the MS industrial complex itself if in 2-3 years time we start seeing dozens if not hundreds of cancers in patients taking Ocrevus? There's also the possibility that opportunistic infections will start taking a toll, as was seen in the lupus and RA trials.

    Will this be the cost that ultimately forces MS researchers to once again start robustly searching for the cause of the disease, rather than spending untold amounts of time and money on finding newer and more sophisticated approaches for suppressing the immune system?

    For progressive patients, is the risk/reward ratio of taking these drugs in the hopes of a moderate (?) decrease in disease progression worth the risk of serious adverse events down the line?

    We are in largely uncharted waters here, let's hope they're not be monsters lurking below…

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    Replies
    1. Agree with your points, it’s important that screening strategies are put in place.

      Re: Ocrelizumab I was aware of the 11 malignancies ~2.3%. 6 of the 781 were breast cancers - a mammogram is going to be necessary here. Maybe these should be used only as induction therapies. For instance Alemtuzumab is 10y down the line with little in the way of malignancies being reported.

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    2. I agree with all your points The Wheelchair Kamikaze.

      What we see is an "academicist struggle," which seems to have no end between "T-cells and B-cells", and meanwhile Big Prharma comes with increasingly potent immunosuppressive drugs, but they leave the following message "Okay, there's the containment of the immune system, but the consequences of that are not our problem."

      Perhaps science in trying to unravel the real cause of MS needs a campaign like that of the ice bucket made for ALS, since it all boils down to the money involved too.

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