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Using HDAC Inhibitors to Overcome Myeloma Treatment Resistance

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New Orleans, LA December 10, 2013 - Monday is "myeloma day" here at ASH.  Non-stop oral presentations about myeloma research from 7 a.m. to 7 p.m.  My day started listening to four presentations focused on overcoming drug resistance.  

It sounds like they're making progress. But I'll be honest. Even though I read and write a lot about multiple myeloma every day, some of the research at the cellular level is way over my head.

Even so, I was able to learn that researchers are now able to overcome myeloma's resistance to proteasome inhibitors (Velcade, Kyprolis, ixazumib) by adding an HDAC inhibitor to the mix.  What the heck is an HDAC inhibitor?  That's where I start to get lost in the specifics.  But an example of a HDAC inhibitor would be panobinostat, a new experimental drug that's in Phase III trials.

Apparently, adding panobinostat to any of the proteasome inhibitors effectively re-sensitizes myeloma resistant cells. In other words, the combination of certain HDAC inhibitors helps drugs like Velcade work again.  

Great news, right?  It's this type of research that has excited myeloma experts for years.  But there's a catch.  This research is being done in mice and human cells in the lab, not in people.  

How is it working in multiple myeloma patients?  Reviews are mixed.  Like a number of other exciting new drugs, the tendency is for them to work better in the lab than in us.  No one is really sure why.  Maybe scientists haven't found just the right mix yet. 

Based on what I've read and experts I've interviewed, panobinostat therapy works.  Here come's that "but" again. There may be a problem getting the drug approved by the FDA.  Why?  Because it doesn't do much by itself.  It needs to be combined with another existing myeloma therapy.  And thus far, the FDA has only approved drugs that show significant single agent activity.  

I'll post more about some of the exciting new therapies being reviewed here at ASH next time.

Until then, feel good and keep smiling!  

-- Pat

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