BETA - What should myeloma patients know about chemo-induced peripheral neuropathy (CIPN)?

What is peripheral neuropathy? Peripheral neuropathy is a broad term. It describes a numbness or tingling, a loss of sensation or pain in the extremities. And in myeloma patients, sometimes it's present diagnosis. Sometimes patients have it from a preexisting condition such as diabetes where their small vessel damage in fingers and toes. What myeloma therapies have been known to cause chemo-induced peripheral neuropathy? One of the mainstays of treatment in myeloma is bortezomib and exazomib, which is a sort of a cousin oral version of bortezomib, I would say. And these drugs can lead to peripheral neuropathy. I think studies across the board using the Revlim and Velcade dexamethasone program with the addition of daratumumab have demonstrated that approximately 50 to 60 percent of patients will develop some form of peripheral neuropathy, typically manifest as numbness in the fingers and toes. About 20 to 30 percent will develop a more significant neuropathy that is limiting, may limit functionality like buttoning a shirt or make it a little bit more challenging to write with a pen. And maybe five to seven percent may develop a more significant peripheral neuropathy that results in the pain and discomfort and can be debilitating. So this is a very important side effect to pay attention to. We've made some adjustments over the years to how we give Velcade initially. It was given intravenously twice weekly. Now it's given subcutaneously. And a once weekly schedule is one that results in the least incidence, the lowest incidence of peripheral neuropathy. We know that a number of the myeloma drugs can cause peripheral neuropathy, particularly Velcade, thalidomide, which is an older immunomodulating drug can cause it. So we're monitoring patients pretty frequently for this as a side effect. When it's a side effect of treatment, it tends to come on slowly and over the course of many Velcade injections. There are people who experience it pretty rapidly. So it's important to determine what exactly is causing it because there are vitamin deficiencies that can lead to it, anemia, as I said, diabetes can cause peripheral neuropathy. And when it's from Velcade, it's important to know because Velcade is a big component especially initially for patients. Exazomib, I can't think of the numbers off the top of my head, but there is less peripheral neuropathy associated with it and same with carfilzomib. So it's always a choice to change to one of those proteasome inhibitors if patients seem to have severe neuropathy from Velcade. So one therapy that we infrequently will use in myeloma is cisplatin. We don't use it a lot of it and don't use it repeatedly, but that is a therapy that also can cause neuropathy. But fortunately in myeloma these days, this is not a treatment that we need to routinely use. What are signs or symptoms of neuropathy that patients should be aware of and discuss with their treating physician? So I think folks initially notice some numbness in the fingers. People will describe a sensation that they're walking in socks even though they're not. So those are the things that you need to alert your physicians to so that they can manage this. I think one of the important things about this neuropathy is that it's important to try to prevent development of severe neuropathy because even when treatment stops, it doesn't necessarily resolve. In fact, it might improve, but oftentimes it does not resolve. There is an alternative proteasome inhibitor, carfilzomib, that carries a different profile of side effects, which does not include neuropathy. So that is also an option for those that have adequate organ function reserve and can tolerate that drug. How is peripheral neuropathy monitored? So we monitor it in clinic by asking questions about how patients' fingers and toes feel. A lot of times people describe like, oh, there's no pain, but it feels like my hands are in gloves or my feet are walking on pebbles all the time. Sheets can be bothersome at night for patients. It can progress to fine motor deficits where using your fingers, well, your fingers don't work as well as they should. Buttoning can be hard. Patients can lose balance because of the loss of sensation in their toes. When there's, seems like severe peripheral neuropathy from treatment or from another cause, I usually have people go see a neurologist, a specialist who can do real fine testing for the nerves and neurons and see exactly what's causing it with the goal to obviously not allow it to progress for people where they become debilitated. So monitoring-wise, I think it has to do with taking a patient history, making sure to ask about it, and from the patient perspective, making sure to describe it and be aware that that's something to watch out for. How is peripheral neuropathy managed? From a treatment perspective, it's generally treated symptomatically, oftentimes with medications like apopentin, which is something that helps relieve neurologic pain, sometimes with types of antidepressant called Cymbalta that also can relieve neuropathic pain. We often will give a B-vitamin complex, aflalipoic acid, and things like that, which can be helpful. They're more supportive. But the best treatment for neuropathy is to avoid it. Continuing to exercise and be active can be helpful for people. There are certain pain medicines that are non-opioid that can help with peripheral neuropathy. They were approved for patients with diabetes who have peripheral neuropathy. One of the most common drugs is called gabapentin. That can be helpful. All it does, though, is decrease the sensation of pain. It doesn't alter the vessel damage that was done by the drug. There are some other atypical medicines, meaning not FDA approved for peripheral neuropathy. I think a lot of people get benefit from Cymbalta or duloxetine, which is typically an antidepressant, but that can help with atypical pain syndromes. Final thoughts on neuropathy. Neuropathy is something that is very, very important to me to know. Some patients have neuropathy in a sense that they say they have a slight tingling which goes away after a while. Neuropathy patients have significant difficulty, cannot walk anymore, have problems sleeping or other issues with neuropathy. The problem is when neuropathy is there, it's very difficult to treat and to get rid of completely. Oftentimes, some patients really have to live the rest of their lives with neuropathy. Thankfully, we have a lot of treatment options for myeloma, so myeloma patients can live long. I always in my mind, I don't want them to live long with neuropathy. As soon as it starts, they should let their physician know. But if it's just myelin, it doesn't really impact quality of life, continuing the treatment or maybe even continuing the treatment with the same dose is very helpful. Sometimes you can dose reduce, sometimes you can stretch out the treatment that is still similarly effective. So definitely communicate with your physician and also let your physician know how much it bothers you. If you say it's not a big deal to me, that's okay. If it really bothers you, you should definitely adjust your treatment. We have a lot of treatment options that we can change to if the neuropathy is bothering them.