Dr. McCarthy,
Of carfilzomib, elotuzumab, perifosine, pomalidomide, panobinostat, and vorinostat, which agent is the most exciting, in your opinion. Further, with science informing clinical trials and increasing the percentage of agents FDA approved in myeloma, do you foresee all of these agents being approved?
Thank you
Forums
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combination therapy
Dear Dr. Carthy,
first thank you for your kind response on our questions. I want to add something to this question. In HIV the combination therapy leaded to a control of the disease. Which agents could be combind togehter. Will be a combination of Carf/Velc/Rev/Dex and Antibody in low doses used in the future?
Thank you, TOM
first thank you for your kind response on our questions. I want to add something to this question. In HIV the combination therapy leaded to a control of the disease. Which agents could be combind togehter. Will be a combination of Carf/Velc/Rev/Dex and Antibody in low doses used in the future?
Thank you, TOM
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thomas l
Re: Exciting new therapies question
Hi Thomas I and Perseverance
First the question regarding combinations. One of the more recent combinations is lenalidomide (Revlimid), bortezomib (Velcade) and dexamethasone (RVD) that was developed at the Dana Farber and generates excellent responses including a fair number of complete responses. This regimen is of great interest and is being compared to transplant in a large French American study I mentioned in a previous posting. The Italian Multiple Myeloma Network has reported excellent results in non-transplant patients with a combination of bortezomib, melphalan prednisone and thalidomide followed by bortezomib and thalidomide maintenance. As the thalidomide can be neurotoxic, they recently reported on the use of melphalan prednisone and lenalidomide, comparing it to melphalan and prednisone with different arms receiving maintenance or not with lenalidomide. They demonstrated excellent results in the lenalidomide arms in terms of progression free survival. There is no difference in overall survival at 3 years which likely reflects the excellent salvage regimens that patients can receive for disease relapse or progression.
I think that carfilzomib may be combined with steroids and a immunomodulatory drug such as lenalidomide but since bortezomib and carfilzomib have similar mechanisms of action they may not be combined. However, this does not mean that sequential use could not be tested. Antibodies against multiple myeloma cells are being tested and show promise especially when combine with other agents. Of note, it is very important that different combinations be tested in clinical trials so as to make sure there is no unexpected side effect that could be unacceptably toxic. Perifostine is a new agent that inhibits a class of kinases which are signalling molecules that help the multiple myeloma cells grow. Elotuzumab is a monoclonal antibody against a cell surface glycoprotein that is expressed on myeloma cells. Of note, while multiple myeloma cells may express the target molecules of these drugs in high amounts, these proteins or enzymes can be expressed in normal cells so it is very important to for close monitoring, thus, the need for clinical trials to test these new agents. So, I cannot really pick a new drug as they likely will all have places as part of induction and salvage therapy.
First the question regarding combinations. One of the more recent combinations is lenalidomide (Revlimid), bortezomib (Velcade) and dexamethasone (RVD) that was developed at the Dana Farber and generates excellent responses including a fair number of complete responses. This regimen is of great interest and is being compared to transplant in a large French American study I mentioned in a previous posting. The Italian Multiple Myeloma Network has reported excellent results in non-transplant patients with a combination of bortezomib, melphalan prednisone and thalidomide followed by bortezomib and thalidomide maintenance. As the thalidomide can be neurotoxic, they recently reported on the use of melphalan prednisone and lenalidomide, comparing it to melphalan and prednisone with different arms receiving maintenance or not with lenalidomide. They demonstrated excellent results in the lenalidomide arms in terms of progression free survival. There is no difference in overall survival at 3 years which likely reflects the excellent salvage regimens that patients can receive for disease relapse or progression.
I think that carfilzomib may be combined with steroids and a immunomodulatory drug such as lenalidomide but since bortezomib and carfilzomib have similar mechanisms of action they may not be combined. However, this does not mean that sequential use could not be tested. Antibodies against multiple myeloma cells are being tested and show promise especially when combine with other agents. Of note, it is very important that different combinations be tested in clinical trials so as to make sure there is no unexpected side effect that could be unacceptably toxic. Perifostine is a new agent that inhibits a class of kinases which are signalling molecules that help the multiple myeloma cells grow. Elotuzumab is a monoclonal antibody against a cell surface glycoprotein that is expressed on myeloma cells. Of note, while multiple myeloma cells may express the target molecules of these drugs in high amounts, these proteins or enzymes can be expressed in normal cells so it is very important to for close monitoring, thus, the need for clinical trials to test these new agents. So, I cannot really pick a new drug as they likely will all have places as part of induction and salvage therapy.
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Dr. Philip McCarthy - Name: Philip McCarthy Jr., M.D.
3 posts
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