Thank you for the layperson-friendly explanations in the forum thread about how multiple myeloma drugs work! I have been reading this forum and the technical talk is like a foreign language. My question is this: How / why do multiple myeloma drugs cause peripheral neuropathy? I literally suffer from that, due to both Revlimid and Kyprolis, and have had to stop both. Unfortunately, the neuropathy pain has worsened. Help with understanding the how and why would be appreciated.
Thank you.
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jgilmore - Name: Yanell
- Who do you know with myeloma?: Me
- When were you/they diagnosed?: 2009
- Age at diagnosis: 57
Re: Why do myeloma drugs cause peripheral neuropathy?
Hi jgilmore,
I can't answer your question about why many myeloma drugs cause peripheral neuropathy. I suspect the mechanism is slightly different for each of the different classes of drugs.
If you're looking for possible solutions to your neuropathy, you'll be glad to hear that there's a lot of discussion of that subject already here in the forum. This link will show you a (long!) list of discussion related to peripheral neuropathy. Many of them are about different options for reducing the discomfort from the condition.
The link that I mentioned above is from this post, which is always pinned to the top of the Treatments & Side Effects section of the forum. It's a good post to remember, since it has links to existing forum discussions about many different treatments and potential side effects of treatment.
Good luck!
I can't answer your question about why many myeloma drugs cause peripheral neuropathy. I suspect the mechanism is slightly different for each of the different classes of drugs.
If you're looking for possible solutions to your neuropathy, you'll be glad to hear that there's a lot of discussion of that subject already here in the forum. This link will show you a (long!) list of discussion related to peripheral neuropathy. Many of them are about different options for reducing the discomfort from the condition.
The link that I mentioned above is from this post, which is always pinned to the top of the Treatments & Side Effects section of the forum. It's a good post to remember, since it has links to existing forum discussions about many different treatments and potential side effects of treatment.
Good luck!
Re: Why do myeloma drugs cause peripheral neuropathy?
Peripheral neuropathy (PN) has been a common side effect of users of the proteasome inhibitor (PI) Velcade. It occurred more often when it used to be given intravenously. A few years ago, they found that it could be administered just as effectively through a subcutaneous shot with the added benefit of reducing the incidence of peripheral neuropathy
Revlimid has also been linked with peripheral neuropathy, but not nearly as often as Velcade. Kyprolis, another proteasome inhibitor, normally is not associated with much peripheral neuropathy. Recently the FDA approved an oral proteasome inhibitor, Ninlaro (ixazomib), but peripheral neuropathy has been listed as a side effect of that drug.
I would suspect that Revlimid is the main culprit in your case. Usually PN will gradually stop after you stop taking the drug. The problem with PN is that it is not a predictable side effect. The majority of users of Velcade and Revlimid have not had an issue with PN. However, the percentage of those that have are significant.
Revlimid has also been linked with peripheral neuropathy, but not nearly as often as Velcade. Kyprolis, another proteasome inhibitor, normally is not associated with much peripheral neuropathy. Recently the FDA approved an oral proteasome inhibitor, Ninlaro (ixazomib), but peripheral neuropathy has been listed as a side effect of that drug.
I would suspect that Revlimid is the main culprit in your case. Usually PN will gradually stop after you stop taking the drug. The problem with PN is that it is not a predictable side effect. The majority of users of Velcade and Revlimid have not had an issue with PN. However, the percentage of those that have are significant.
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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: Why do myeloma drugs cause peripheral neuropathy?
Some of the suspected causes of peripheral neuropathy due to proteasome inhibitors such as Velcade are complex and don't really lend themselves to simple explanations. See one such complex explanation here:
Argyriou, AA, et al, "Bortezomib-induced peripheral neurotoxicity: an update," Archives of Toxicology, Sep 2014 (abstract)
Suffice it to say that several of the drugs used to treat myeloma are neurotoxic and can damage the nerves themselves, resulting in peripheral neuropathy.
This was a good series of articles that the Beacon did on peripheral neuropathy back in 2012:
https://myelomabeacon.org/news/2012/03/26/drug-induced-peripheral-neuropathy-in-multiple-myeloma-patients-part-1-what-is-it-and-who-is-at-risk/
https://myelomabeacon.org/news/2012/03/30/drug-induced-peripheral-neuropathy-in-multiple-myeloma-patients-part-2-treatment/
https://myelomabeacon.org/news/2012/04/02/drug-induced-peripheral-neuropathy-in-multiple-myeloma-patients-part-3-prevention-and-future-directions/
Argyriou, AA, et al, "Bortezomib-induced peripheral neurotoxicity: an update," Archives of Toxicology, Sep 2014 (abstract)
Suffice it to say that several of the drugs used to treat myeloma are neurotoxic and can damage the nerves themselves, resulting in peripheral neuropathy.
This was a good series of articles that the Beacon did on peripheral neuropathy back in 2012:
https://myelomabeacon.org/news/2012/03/26/drug-induced-peripheral-neuropathy-in-multiple-myeloma-patients-part-1-what-is-it-and-who-is-at-risk/
https://myelomabeacon.org/news/2012/03/30/drug-induced-peripheral-neuropathy-in-multiple-myeloma-patients-part-2-treatment/
https://myelomabeacon.org/news/2012/04/02/drug-induced-peripheral-neuropathy-in-multiple-myeloma-patients-part-3-prevention-and-future-directions/
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Multibilly - Name: Multibilly
- Who do you know with myeloma?: Me
- When were you/they diagnosed?: Smoldering, Nov, 2012
Re: Why do myeloma drugs cause peripheral neuropathy?
Thanks for this thread about neurotoxic drugs that can cause peripheral neuropathy. It was interesting to re-read the three articles written in 2012 on this topic; thanks for posting them, Multibilly.
The quote from the first article, especially about second generation proteasome inhibitors, seemed hopeful in getting drugs that cause less neuropathy than thalidomide, or to a lesser but still sometimes severe neuropathy as Velcade (bortezomib). As Ron noted, peripheral neuropathy is less when Velcade is administered by subcutaneous injection. When I had Velcade, it was by IV, and even after a few cycles of that, I developed mild neuropathy in the feet, which is still with me! I am always queried about this every time I have an appointment with my oncologist.
"Much lower rates of peripheral neuropathy have been reported in myeloma patients treated with Revlimid (up to 2 percent severe neuropathy) and pomalidomide (preliminary data suggests low to intermediates rates).
Moreover, recent studies have shown patients taking carfilzomib (Kyprolis), marizomib, and MLN9708 (ixazomib) – which belong to the same class of drugs as Velcade, called proteasome inhibitors – may also experience lower rates of peripheral neuropathy.
'Second generation proteasome inhibitors such as carfilzomib, marizomib, and MLN9708 are significantly less neurotoxic and also show considerable therapeutic promise, especially carfilzomib and MLN9708,' said Dr. Richardson.
However, the experts acknowledged that larger studies are needed to confirm the rate of peripheral neuropathy in patients receiving these newer proteasome inhibitors."
The quote from the first article, especially about second generation proteasome inhibitors, seemed hopeful in getting drugs that cause less neuropathy than thalidomide, or to a lesser but still sometimes severe neuropathy as Velcade (bortezomib). As Ron noted, peripheral neuropathy is less when Velcade is administered by subcutaneous injection. When I had Velcade, it was by IV, and even after a few cycles of that, I developed mild neuropathy in the feet, which is still with me! I am always queried about this every time I have an appointment with my oncologist.
"Much lower rates of peripheral neuropathy have been reported in myeloma patients treated with Revlimid (up to 2 percent severe neuropathy) and pomalidomide (preliminary data suggests low to intermediates rates).
Moreover, recent studies have shown patients taking carfilzomib (Kyprolis), marizomib, and MLN9708 (ixazomib) – which belong to the same class of drugs as Velcade, called proteasome inhibitors – may also experience lower rates of peripheral neuropathy.
'Second generation proteasome inhibitors such as carfilzomib, marizomib, and MLN9708 are significantly less neurotoxic and also show considerable therapeutic promise, especially carfilzomib and MLN9708,' said Dr. Richardson.
However, the experts acknowledged that larger studies are needed to confirm the rate of peripheral neuropathy in patients receiving these newer proteasome inhibitors."
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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: Why do myeloma drugs cause peripheral neuropathy?
Many thanks to all of you for sharing your experiences, articles, and for the discussion.
My peripheral neuropathy emerged while I was on Revlimid maintenance (5 mg) after my first autologous stem cell transplant (ASCT) in July 2009, and worsened while on Kyprolis (carfizomib) maintenance after ASCT #2 in October 2015.
Here's an additional wrinkle: I visited my PC physician this past week. When she examined my toes, which were cold and blue inspire of the socks and boots I wore) she said that I also had Raynaud's phenomenon. She advised that it was imperative that I keep my hands and feet warm.
Observing the pain since my peripheral neuropathy visit, I surmise that if my feet are cold and painful, it's the Raynaud's; and if they're painful but not cold, it's the peripheral neuropathy. I wonder if Raunaud's is related to multiple myeloma.
Still looking for a solution to the almost ever present pain. Thanks again for the discussion.
My peripheral neuropathy emerged while I was on Revlimid maintenance (5 mg) after my first autologous stem cell transplant (ASCT) in July 2009, and worsened while on Kyprolis (carfizomib) maintenance after ASCT #2 in October 2015.
Here's an additional wrinkle: I visited my PC physician this past week. When she examined my toes, which were cold and blue inspire of the socks and boots I wore) she said that I also had Raynaud's phenomenon. She advised that it was imperative that I keep my hands and feet warm.
Observing the pain since my peripheral neuropathy visit, I surmise that if my feet are cold and painful, it's the Raynaud's; and if they're painful but not cold, it's the peripheral neuropathy. I wonder if Raunaud's is related to multiple myeloma.
Still looking for a solution to the almost ever present pain. Thanks again for the discussion.
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jgilmore - Name: Yanell
- Who do you know with myeloma?: Me
- When were you/they diagnosed?: 2009
- Age at diagnosis: 57
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