- Elotuzumab is a laboratory-manufactured monoclonal antibody which works against a cell surface glycoprotein, CS1, highly expressed in multiple myeloma (MM). Like the antibodies that our own bodies produce, it attaches to the target protein and kills or disables the cell possessing that protein. It has been tested successfully in Phase I and II trials with both Velcade and Revlimid. In the Revlimid trial, 28 patients with lots of prior therapies experienced an overall response rate of 82%. Not bad. I personally believe that many more monoclonal antibodies are in our future - these are the "silver bullets," highly-directed therapy that really could make myeloma a chronic disease. Someday, not yet.
By the way - the suffix "mab" on the generic drug name elotuzumab means "Monoclonal AntiBody." We'll see more MABs.
- Denosumab (see - here's another) is also a monoclonal antibody, this time directed at a signal protein which promotes bone removal. Thus denosumab inhibits destruction of bones by myeloma and its treatments. This is cool stuff. Several Phase III studies were reported at ASCO, all of them showing an advantage for denosumab over Zometa. Quoting the conclusion of one study (9042), which included myeloma patients: "In this head-to-head study, patients receiving denosumab had longer time to first skeletal-related event (SRE) or hypercalcemia and time to radiation to bone compared with Zometa. A lower proportion of patients experienced an on-study SRE in the denosumab group compared with Zometa." In another study, patients taking denosumab experienced less bone pain than those taking Zometa.
- Vorinostat, brand name Zolinza, is already approved for some cancers. It is a new class of drug called histone deacetylase (HDAC) inhibitors. I don't know what means, actually, except that it works by a different mechanism than Revlimid, Velcade, melphalan, or dexamethasone, making it an excellent candidate for use WITH those drugs. So far it looks promising in early studies with both Velcade and Revlimid. Another HDAC inhibitor, panobinostat, also shows promise.
Nice salmon dinner aboard the Amtrak Empire Builder:
Hi Don, thanks for reporting on the conference for those of us who were unable to attend. Great job!
ReplyDeleteI have to say, however, that I don't think denosumab is cool stuff at all.
I wrote two posts (in October 2009)denouncing denosumab. By pure chance, I unearthed information that did NOT come directly from the producer of this drug (as many medical websites did, unfortunately...they based their info on the company's PRESS RELEASE, for Pete's sake...), such as http://www.medpagetoday.com/ProductAlert/Prescriptions/15486 So denosumab has lots of bad side effects. You can do a search of my blog for more details. Anyway, denosumab gives me a very BAD case of the jitters...but of course I am not surprised to learn that it is being promoted at a conference such as ASCO...it all boils down to money, of course...
Hi Margaret,
ReplyDeleteThanks for the comment! I went to that web site and see what you mean.
But a myelomiac with bones that are broken and full of holes needs something, and a bisphosphonate like Zometa has its own risks, including kidney damage.
I just think that monoclonal antibodies are cool technology, even if denosumab doesn't turn out to be :-)
Take care
You are absolutely right, Don. I just wish that the focus were on non-toxic substances, not on these toxic drugs that, however, line the pockets of the big pharmaceutical companies.
ReplyDeleteI mean, there are substances whose natural bone-healing/protecting qualities could undoubtedly be enhanced and improved in a lab setting. For instance, curcumin(speaking of which, my one regret is that I didn't have a bone density test BEFORE taking curcumin...I have super strong/thick bones, but I don't know how they were in the pre-curcumin period...bummer!), but I have also come across a few others in my research...
It's just so frustrating when you think of all the waste and greed...not to speak of the manipulation of clinical trials (remember this SD article: http://www.sciencedaily.com/releases/2010/05/100507092335.htm ?) and so on...while there are patients who could really benefit from these natural extracts right NOW...eh...
Yup - one of the ASCO speakers pointed out how hard it is to get a natural substance approved for use, with lack of funding and intellectual property issues and whatnot.
ReplyDeleteBut you are correct - what about Vitamins K2 and D3, which have been shown to rebuild bones? I take those myself, every day, and my latest bone density measurement apparently showed no loss of bone in the last three years (different machine three years ago, so results were not identical).
Thanks for your comment.
Margaret & Don,
ReplyDeleteI'm an inflammatory breast cancer patient, now NED, taking an aromatase inhibitor to prevent recurrence. To offset the bone-loss side effects from the AI, I'm taking an oral bisphosphonate. I was thinking of moving to IV bisphos, but heard about denosumab today and am wondering if it would be a better choice for me. Your blog comments have made me re-considering. Margaret, I wanted to look up the info in your blog, but could not figure out how to access it. Can you please help me?
Hi Brenda, this is my blog's URL: http://margaret.healthblogs.org/
ReplyDeleteThere is a Search box on the right: just scroll down my Pages, almost to the end. If that doesn't work, drop me a note via my Contact form. :-)
Margaret
Hi Brenda,
ReplyDeleteI don't think there is a really good choice! All of the bisphosphonates have side effects, some fairly serious, and denosumab apparently can too. But you sure don't want fragile, broken bones either!
I might suggest, whatever you choose, to be sure to get enough calcium along with vitamin K2 (not full-spectrum K) and vitamin D3.
Studies have shown that calcium citrate works better than calcium carbonate if you don't happen to take the calcium carbonate with a meal.
Best to you.