Promising Oral Myeloma Therapies

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Topics include: Treatments

Where do we stand with oral therapies in development to treat myeloma? Dr. Paul Richardson, an expert from the Dana-Farber Cancer Institute, provides an overview of oral proteasome inhibitor treatments currently in trials and their potential impact on survival and quality of life. Dr. Richardson is joined by Jim Omel, a patient advocate and physician, who shares his thoughts on the benefits of oral therapy for people with myeloma.

Made possible through an educational grant from the Patient Empowerment Network, which received support from Millennium: The Takeda Oncology Company.

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Please remember the opinions expressed on Patient Power are not necessarily the views of Dana-Farber Cancer Institute, its medical staff 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.

Andrew Schorr:
Hello and welcome to Patient Power. I’m Andrew Schorr.  Joining us are two people who know a lot about myeloma—that’s Dr. Jim Omel from Nebraska, who’s a physician, but also has been a myeloma patient since 1997, and is a very active patient advocate.

And, of course, welcome back to Patient Power, Dr. Paul Richardson, who is the clinical director of the myeloma program at the Dana-Farber Cancer Institute in Boston. Dr. Richardson, I wanted to start with you and get an update on oral therapy for myeloma.

There’s been a lot of new data coming out, more to come, and you are very involved in the trials. Where are we now, Dr. Richardson, with oral therapy?

Dr. Richardson:     

Well, thank you very much Andrew, I think where we are with oral therapies and myeloma is really the excitement of the original immunomodulator platform that was first provided by thalidomide, then lenalidomide, and most recently, by pomalidomide, can now be added to by the availability of orally bio-available proteasome inhibitors.

And there are several currently under study. The one that is in the most advanced stage of development is ixazomib, also known as MLN9708, and this is the first in class boronate peptide administered either weekly or twice weekly, which is remarkably active in myeloma therapy, and also, excitingly, is generally well tolerated.

It seems to lack the neurotoxicity that we sometimes see with bortezomib, its IV counterpart or sub-cu counterpart, I should say, and it doesn’t seem to have other serious side effects that can sometimes be associated with other proteasome inhibitors as well.

Having said that, it can be associated with some skin rash, which generally proves manageable, and also, occasionally, some upper and lower gastrointestinal discomfort, but again, the symptoms that it causes, typically, are manageable with supportive care.

So with the platform of, of the oral proteasome inhibitor ixazomib now established from Phase I and II studies in relapsed refractory disease, the excitement, really, Andrew, has been to combine it with the IMiDs and, of course, lenalidomide has been the first dance partner in this.

And so, the combination of ixazomib, lenalidomide, and dexamethasone, or actually, as we call it, RID, R-I-D, Revlimid, ixazomib, dexamethasone; the RID regimen has now become, really, quite exciting, because we’ve moved it into the upfront treatment of myeloma.


And what we’ve seen there, Andrew, is that when you use these three drugs together, in the initial treatment of myeloma, we have response rates in excess of 90 percent. 

They’re actually 95 percent overall so ,essentially, very similar to what we see with either bortezomib, lenalidomide and dexamethasone or Carfilzomib, lenalidomide and dexamethasone, which generate very high quality responses.


And what’s so exciting is that this all oral regimen seems to be about the same in terms of efficacy and, also excitingly, it seems to be generally well tolerated.

Now, there are other oral agents in development coming along as well, correct?

Dr. Richardson:
Well, right, and there are other proteasome inhibitors that are undergoing testing that are already bio-available. Just as Ixazomib is the oral counterpart of bortezomib, so there is a new drug called oprozomib, which is the counterpart of IV carfilzomib.

And oprozomib is very exciting because it’s a very potent proteasome inhibitor.

And it, too, does appear to be tolerable in terms of an oral approach to medication, although whilst it isn’t associated with skin rash in the way that ixazomib is, oprozomib does, unfortunately, seem to have significant gastrointestinal side effects which we’re in the process of working on to improve tolerability and get to a point where this drug could be well tolerated.

And I think, generally speaking, I’m very pleased. I think we’re making progress in that regard, so the real prospect is of a whole array of different proteasome inhibitors that are already bio-available that can help patients.


Jim, I want to ask you your perspective as a patient, but, also, I know you’re on the Myeloma Steering Committee with the National Cancer Institute related to clinical trials. So here we have seen the transition from chemotherapy, with some really heavy-duty drugs, to pills that can make a real difference.

We’ve had a number of pills, and now we have, even in other classes, proteasome inhibitors coming along. What do you think this means for patients?

Dr. Omel:      

I just see this as an exciting development, Andrew. If you can imagine, from a patient’s standpoint, having to go to the clinic and then perhaps cut back the next day for the same treatment, if you’re living a long ways from the cancer center, that gets to be quite a burden.

And imagine the difference between that versus taking a pill, taking a capsule with the direction of your physician. It’s just a world of difference between those two treatments.

Dr. Richardson:
No, Jim, I so agree. I think that what we’ve seen, Andrew, amongst our patients is a real enthusiasm, because at the end of the day, probably the most tolerable and active combination of ixazomib, lenalidomide and dexamethasone has been the use of ixazomib once a week with lenalidomide given in the traditional fashion.

And, you know, compliance with that regimen has been superb, so I would echo Jim’s comments that this ability to have all oral regiment that’s so active without the inconvenience of having to go to the infusion center every, you know, several times a week is a huge bonus.

Dr. Omel:   
Much, much different.

Well, it’s great to hear the news that the effectiveness you’re seeing as part of clinical investigation.

We’ll look for updates on that, Dr. Richardson and I know, Jim Omel, you and the patient community wait with bated breath to see how all this pans out, and hopefully, benefits many other people to come. I want to thank both of you for being with us, Jim Omel, thank you and we wish you continued good health. And Dr. Paul Richardson, thank you for your devotion in your work with patients.

Dr. Richardson:       

Thank you Andrew, very much.

Dr. Omel:
Thank you Andrew, very much, yes.

I’m Andrew Schorr. Thank you for joining us. Remember, knowledge can be the best medicine of all.

Please remember the opinions expressed on Patient Power are not necessarily the views of Dana-Farber Cancer Institute, its medical staff 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 March 31, 2014