Cyclophosphamide treatment for severe MS

#MSBlog Treating MS with a sledgehammer!

High dose cyclophosphamide (HiCY) without stem cell rescue has been shown to induce remissions in people with severe autoimmune disorders (SADS). However, up to 80% of these people ultimately relapse. Here these investigators review the outcomes of seven people treated with two cycles and one person  treated with three cycles of HiCY. The diseases re-treated were scleroderma, MS, three people with severe aplastic anemia (SAA), and three people with myasthenia gravis (MG). All but two with SAA had received standard immunomodulatory therapy for their disease up front and had been refractory. All people had complete hematologic recovery. Overall survival in this cohort was 100%. All subjects relapsed after the initial cycle but event free survival thereafter was 93.3%. All are still in remission except two people with MG, one of whom relapsed after a severe GI infection requiring hospitalization, and the other relapsed 3 years after the second treatment and she did not respond to the third treatment. This shows that HiCY can be safely re-administered in people with SAA and refractory SADS. The quality and duration of second remissions appears to be equal or superior to the first remission.

“High-dose cyclophosphamide, short of immunoablative autologous bone marrow transplantation, is one of the most powerful immune system rebooters used in MS. It is associated with serious bone marrow suppression and MSers treated in this way are at high risk of infections and bleeding. Most MSers need to spend several weeks in or close to a hospital to have bone marrow support. In addition, it causes severe hair loss, which is transient, mucositis (sloughing and ulceration of the lining of mouth) and most woman who have this treatment develop ovarian failure (premature menopause). Once we have the option of using alemtuzumab I doubt anybody will take the acute or short-term risks of cyclophosphamide treatment. Would you?”

“The late John Newsom-Davis, the Professor of Neurology at Oxford, used to query the need for using various sledgehammers to treat autoimmunity. I am beginning to think he was right. We need a more targeted approach. Maybe the Charcot Project will surprise us.”

7 thoughts on “Cyclophosphamide treatment for severe MS”

  1. Some people consider even alemtuzumab too much of a sledgehammerWill alemtuzumab have the same effect on these patients? If it will, there should be some way for them to get it in advance of approval.What options do such patients have if they can't get alemtuzumab?Is there also a low dose cyclophosphamide? How well does that work?

    1. Alemtuzumab has now been withdrawn from the market in preparation for the launch of the MS version called Lemtrada. At present you can't get Lemtrada. Cyclophosphamide is not licensed for MS and is only used in very special cases; highly active MSers who have failed other therapies.

  2. I don't believe that such a sophisticated organ as the brain will ever be cured by crude 'sledgehammer' approaches; on the contrary – one needs an equally refined solution.

  3. I think that there is a version of cyclophosphamide called cytoxan that is used at pulsed intervals. HiCy has been used a lot in trials in the US under the name Revimmune and then Cyrevia, I think.I'm sure that in the future there will be much better targeted treatments for MS, but for those with active aggressive disease, the sledgehammer is all there is.

  4. Is this true for every kind of Cyclophosphamide or only for the IV route?There are also tablets availible.

    1. Yes, there are tablets but they have not been tested in MS and are associated with a higher risk of bladder cancer. We rarely use oral tablets in neurology.

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