One of the abstracts presented at ASH really caught my attention. Abstract 487 on HIV protease inhibitor nelfinavir, when combined with Velcade and Dex has excellent activity in patients that are refractory to Velcade and Revlimid.
For patients that become refractory to the proteasome Inhibitor Velcade the prognosis is not very good, especially if they are double refectory to both Velcade and Revlimid. Generally these patients do not survive long.
The report on this clinical trial was with 34 heavily pretreated patients that were proteasome inhibitor refractory multiple myeloma and 76% were also refractory to Revlimid or double refractory. With this group the trial resulted in an overall response rate of 65% and 69% with the double refractory group. The drug nelfinavir appears to re-sensitize multiple myeloma to both Velcade and Revlimid allowing those agents to become active again. That offers a lot of hope for patients that have become refractory to both drugs.
This was a small test and more must follow but it is very encouraging. The best news is that nelfinavir is an approved drug for HIV is just has not been used with multiple myeloma before.
Here is the link:
Driessen, C., et al, "The HIV Protease Inhibitor Nelfinavir in Combination with Bortezomib and Dexamethasone (NVd) Has Excellent Activity in Patients with Advanced, Proteasome Inhibitor-Refractory Multiple Myeloma: A Multicenter Phase II Trial (SAKK 39/13)," ASH 2016 abstract 487
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Ron Harvot - Name: Ron Harvot
- Who do you know with myeloma?: Myself
- When were you/they diagnosed?: Feb 2009
- Age at diagnosis: 56
Re: ASH 2016 - HIV drug for double refractory patients
I looked up nelfinavir on Wikipedia, and it is an antiretroviral drug. Retroviruses can cause HIV / AIDS. This drug is also being investigated in the US in anti-cancer trials. The abstract shown at ASH was by Swiss researchers. It is a 'protease inhibitor'. Would anyone have any guesses as to why this drug would help patients to be able to take Velcade (bortezomib) for myeloma, whereas previously they had been refractory to it?
From Wikipedia:
Since 2009, nelfinavir has been under investigation for potential use as an anti-cancer agent. When applied to cancer cells in culture (in vitro), it can inhibit the growth of a variety cancer types and can trigger cell death (apoptosis). When Nelfinavir was given to laboratory mice with tumors of the prostate or of the brain, it could suppress tumor growth in these animals. At the cellular level, nelfinavir exerts multiple effects to inhibit cancer growth; the two main ones appear to be inhibition of the Akt/PKB signaling pathway and activation of endoplasmic reticulum stress with subsequent unfolded protein response
In the United States, about three dozen clinical trials are being conducted (or have been completed) in order to determine whether nelfinavir is effective as a cancer therapeutic agent in humans. In some of these trials, nelfinavir is used alone in monotherapy fashion, whereas in others it is combined with other modes of cancer therapy, such as well-established chemotherapeutic agents or radiation therapy.
As of April 2016, no phase 3 cancer trials are registered.
From Wikipedia:
Since 2009, nelfinavir has been under investigation for potential use as an anti-cancer agent. When applied to cancer cells in culture (in vitro), it can inhibit the growth of a variety cancer types and can trigger cell death (apoptosis). When Nelfinavir was given to laboratory mice with tumors of the prostate or of the brain, it could suppress tumor growth in these animals. At the cellular level, nelfinavir exerts multiple effects to inhibit cancer growth; the two main ones appear to be inhibition of the Akt/PKB signaling pathway and activation of endoplasmic reticulum stress with subsequent unfolded protein response
In the United States, about three dozen clinical trials are being conducted (or have been completed) in order to determine whether nelfinavir is effective as a cancer therapeutic agent in humans. In some of these trials, nelfinavir is used alone in monotherapy fashion, whereas in others it is combined with other modes of cancer therapy, such as well-established chemotherapeutic agents or radiation therapy.
As of April 2016, no phase 3 cancer trials are registered.
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Nancy Shamanna - Name: Nancy Shamanna
- Who do you know with myeloma?: Self and others too
- When were you/they diagnosed?: July 2009
Re: ASH 2016 - HIV drug for double refractory patients
Ron,
Isn't Darzalex (daratumumab) supposed to have the same capability, that is, to cause Velcade and Revlimid to again be effective in previously refractory patients?
Just an FYI, I am del 17p and refractory to both Velcade and Revlimid. Unfortunately, Darzalex didn't work for me at all – a dismal failure. Fortunately, Empliciti (elotuzumab) combined with Pomalyst and steroids has been a miracle!
Nancy, I love the fact that people like you are at this site! Your question is so obvious, yet I completely missed. How indeed can an HIV retrovirus be a PI?
Isn't Darzalex (daratumumab) supposed to have the same capability, that is, to cause Velcade and Revlimid to again be effective in previously refractory patients?
Just an FYI, I am del 17p and refractory to both Velcade and Revlimid. Unfortunately, Darzalex didn't work for me at all – a dismal failure. Fortunately, Empliciti (elotuzumab) combined with Pomalyst and steroids has been a miracle!
Nancy, I love the fact that people like you are at this site! Your question is so obvious, yet I completely missed. How indeed can an HIV retrovirus be a PI?
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DanielR - Name: Daniel Riebow
- Who do you know with myeloma?: Self
- When were you/they diagnosed?: 12/2012
- Age at diagnosis: 59
Re: ASH 2016 - HIV drug for double refractory patients
DanielR,
Glad to hear you have found a drug combination that is working so well for you. How long have you been on the Empliciti?
Glad to hear you have found a drug combination that is working so well for you. How long have you been on the Empliciti?
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Melpen - Name: Melissa
- Who do you know with myeloma?: myself
- When were you/they diagnosed?: Feb 5, 2014
- Age at diagnosis: 57
Re: ASH 2016 - HIV drug for double refractory patients
Daniel,
I didn't mean that the HIV drug, nelfinavir, was a PI (proteasome inhibitor). It is a 'protease inhibitor', which I know is different from a PI. I will try to read up on that more too.
I didn't mean that the HIV drug, nelfinavir, was a PI (proteasome inhibitor). It is a 'protease inhibitor', which I know is different from a PI. I will try to read up on that more too.
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Nancy Shamanna - Name: Nancy Shamanna
- Who do you know with myeloma?: Self and others too
- When were you/they diagnosed?: July 2009
Re: ASH 2016 - HIV drug for double refractory patients
Here is a lay explanation of the interaction of the two from Wikipedia:
Proteasomes are protein complexes inside all eukaryotes and archaea, and in some bacteria. ... The main function of the proteasome is to degrade unneeded or damaged proteins by proteolysis, a chemical reaction that breaks peptide bonds. Enzymes that help such reactions are called proteases.
Proteasomes are protein complexes inside all eukaryotes and archaea, and in some bacteria. ... The main function of the proteasome is to degrade unneeded or damaged proteins by proteolysis, a chemical reaction that breaks peptide bonds. Enzymes that help such reactions are called proteases.
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Ron Harvot - Name: Ron Harvot
- Who do you know with myeloma?: Myself
- When were you/they diagnosed?: Feb 2009
- Age at diagnosis: 56
Re: ASH 2016 - HIV drug for double refractory patients
J Cell Commun Signal. 2011 Jun; 5(2): 101–110.
Published online 2011 Jan 31. doi: 10.1007/s12079-011-0121-7
PMCID: PMC3088792
I found a very comprehensive article about proteasome inhibitors. As well as bortezemib, there is carfilzomib (Kyprolis), and others. The proteasome, being the 'garbage can' of the nucleus, degrades proteins, with the help of proteases, into their amino acid components. Then new proteins can be built up. it is a form of 'recycling' in the cell. If the proteasome functions are disrupted, the waste proteins build up and choke the cell, causing cell death. Because cancer cells grow more quickly than normal cells, they can be the target of PI's.
Published online 2011 Jan 31. doi: 10.1007/s12079-011-0121-7
PMCID: PMC3088792
I found a very comprehensive article about proteasome inhibitors. As well as bortezemib, there is carfilzomib (Kyprolis), and others. The proteasome, being the 'garbage can' of the nucleus, degrades proteins, with the help of proteases, into their amino acid components. Then new proteins can be built up. it is a form of 'recycling' in the cell. If the proteasome functions are disrupted, the waste proteins build up and choke the cell, causing cell death. Because cancer cells grow more quickly than normal cells, they can be the target of PI's.
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Nancy Shamanna - Name: Nancy Shamanna
- Who do you know with myeloma?: Self and others too
- When were you/they diagnosed?: July 2009
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