Friday, December 5, 2014

Leukaemia risk from mitoxantrone: higher than previously reported

"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.'"

"Just as 'video killed the radio star'
new DMTs kill older therapies. We mustn't forget that the relentless
drive of innovation is changing the face of MS management. Don't expect
innovation to stop the MS development pipeline is deep and rich, which is why I am such an optimist."

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. 

Methods: We re-evaluated the literature, identifying all case reports and series of > 50 patients reporting TRAL cases in MS. 

Results: TRAL was diagnosed in
0.73% of the 12,896 MSers identified. Median onset was 22 months
following treatment. We calculated a number needed to harm of 137.5
exposed MSers, significantly higher than our 2008 analysis. We found
that 82.8% of MSers were exposed to > 60 mg/m2 with a relative risk
of 1.85 (p = 0.018) compared to < 60mg/m2, strongly suggesting a
relationship to dose. 

Conclusion: MS treatment regimens which limit the mitoxantrone dose to < 60mg/m2 reduce the risk of TRAL.


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