“All the discussion now days, when we discuss DMTs in MS, is risk benefit. One of the more risky drugs that is licensed in several countries for treating MS, is the chemotherapy agent, mitoxantrone. This drug works by inhibiting an enzyme that unzips DNA and causes mistakes when the DNA strands are spliced and stitched back together. As a result of the mistakes, mitoxantrone causes a specific kind of treatment-related leukaemia. This meta-analysis shows that the risk is higher than previously reported and occurs in 1 in 137 MSers treated. I suspect the risk is actually lower than this due to reporting bias; i.e. reports are more likely to pick up leukaemia cases. Despite this, this figure is very high. This sort of leukaemia has a mortality of ~50%. Hence would you be prepared to take the risk of developing leukaemia and death associated with this treatment? Prior to natalizumab and fingolimod arriving on the market we had little option but to offer mitoxantrone to MSers with breakthrough disease that was highly active. As a result of the new drugs we have virtually stopped using this drug. We also had to stop our trial to get rid of NABs to interferon-beta because it included a single dose of mitoixantrone. When you mentioned to potential trial subjects the risk of leukaemia and mentioned that it would potentially put them at high risk of developing PML if they went onto natalizumab they said ‘Thanks, but no thanks.'”
Epub: Ellis et al. Therapy-related acute leukaemia with mitoxantrone: Four years on, what is the risk and can it be limited? Mult Scler. 2014 Jul .
Background: Therapy-related acute leukaemia (TRAL) is a significant concern, when considering treatment with mitoxantrone for MS.