Overcoming Myeloma Resistance to Proteasome Inhibitors with Histone Deacetylase Inhibition

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Topics include: Treatments

Through genetic mutation, multiple myeloma can be a resilient disease, even in the face of the newest proteasome inhibitor therapy. Could the addition of another class of drug help knock out the ability of the myeloma to mutate, allowing other drugs to kill the cancer cells? In this video, recorded on location at ASCO 2014, Dr. Paul Richardson reveals the results of the PANORAMA-1 trial, a large, randomized, multi-center Phase III trial where a histone deacetylase (HDAC) inhibitor, namely panobinostat (LBH589), was added to a regimen of bortezomib and dexamethasone.

Editor’s Note: On February 23, 2015, the U.S. Food and Drug Administration (FDA) gave accelerated approval to panobinostat (FARYDAK) for use in combination with bortezomib and dexamethasone to treat multiple myeloma patients who have received at least two prior regimens.

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Transcript

Please remember the opinions expressed on Patient Power are not necessarily the views of our sponsors, contributors, partners or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you.

Carol Preston:

Hello and welcome to Patient Power. I’m Carol Preston, on location in Chicago, at ASCO 2014, the American Society of Clinical Oncology. Lots of activity here this week and lots of new information on the latest treatments for myeloma. I am joined by a myeloma expert from the Dana-Farber Institute in Boston, Dr. Paul Richardson. Dr. Richardson, thank you for joining us.

Dr. Richardson:

Thank you very much, Carol. First and foremost, it’s a pleasure to join you here for Patient Power. It’s what we consider a fantastic access for patients to get information on the latest advances.

I think very importantly at this meeting in addition to what I’ve just alluded to, the excitement around monoclonal antibodies, the ongoing progress in the DETERMINATION trial, is also some other data from newer drugs that have just really found themselves, if you will, in the context of some positive Phase III results. Probably the one I’d love to share with your audience the most is the combination of panobinostat, bortezomib (Velcade) and dexamethasone (Decadron). This three-drug combination exploits the concept that histone deacetylase inhibition can enhance the efficacy of bortezomib-based proteasome inhibition and overcome resistance.

The concept is that these histone deacetylase inhibitors can work on the adversial risk of the cytogenetics of the myeloma in a way that changes the myeloma’s ability to be resistant and mutationally driven. These drugs can actually not only have a direct anti-myeloma effect in combination with the proteasome inhibitors and, for that matter, also IMiDs, but moreover, they can stabilize instability, if you will, in the genetics of the cancer itself.

Well, it is, and the results of the PANORAMA-1 trial, which we presented today are so important because what they showed was, in a large, over 700-patient study, where patients received panobinostat, bortezomib and dexamethasone versus the control treatment which is bortezomib and dex, we showed highly significant progression free survival advantage, in favor of the three drugs. This was a study conducted in over 20 countries at multiple centers, over 300 centers. It was a very big effort internationally. What’s exciting about that, Carol, is that it’s showing you that we’re trying to bring treatments to the global myeloma community, not, of course, just to the United States. In that context, it’s very exciting to see a series of positive Phase III trials, because this one, in particular, panobinostat plus bortezomib and dex, we hope will lead to an FDA approval for those. That will, obviously, rapidly accelerate access to this important new drug.

Carol Preston:

Dr. Paul Richardson, thank you. Obviously the breakthroughs and treatments in myeloma, it’s breaktaking just to listen to you discuss them. More on it as ASH and later again at ASCO. Thank you so much for joining us.

Dr. Richardson:

My pleasure. 

Carol Preston:

I’m Carol Preston for Patient Power, on-location in Chicago at ASCO 2014. And remember, knowledge can be the best medicine of all.      

Please remember the opinions expressed on Patient Power are not necessarily the views of our sponsors, contributors, partners or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you.

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Page last updated on February 26, 2015