Are Side Effects Impacting Your Quality of Life?
What Patients and Caregivers Need to Know About Side Effect Management and Living Well with Myeloma
- Kevin Brigle, PhD, ANP (VCU Massey Cancer Center, IMF Nurse Leadership Board)
- Beth Faiman, PhD, MSN, APRN-BC, AOCN®, FAAN (Cleveland Clinic – Taussig Cancer Institute, IMF Nurse Leadership Board)
What to Expect
The webinar opens with Kevin Brigle discussing the Scope of the Problem: Definition of Side Effects and Impact on Current, Future Treatment. He will define and outline some common side effects and their impact on current and future myeloma treatments.
In the segment, What Are Some of the Newer Drugs and Their Side Effects?, Beth Faiman reviews recently approved treatments - indications, combinations, and methods of administration (oral, IV, or cellular therapy).
Next, Beth Faiman and Kevin Brigle elaborates on ways that myeloma patients can discuss side effects with their own healthcare teams in How Should You Communicate Side Effects to Your Health Care Team?
If you missed the webinar, watch a replay now with participants' questions at the end. Click the play button on the image at the top of this page to watch now!
Select the section title to view the transcription.
- Good afternoon and good evening, everyone. I'm Robin Tuohy, Vice President Support Groups of the International Myeloma Foundation. And it's my pleasure to welcome you to tonight's educational webinar, living well, focusing on your side effects, are they impacting your quality of life? The goal tonight is to help you learn more and have better discussions to manage those side effects, including peripheral neuropathy, which we know can be a challenge for so many of you out there.
So we of course want to thank our sponsors tonight. And those sponsors of this educational program are Bristol Myers Squibb, Janssen Oncology, and Takeda Oncology. We always appreciate their support. And the next slide is just a quick little reminder for everyone that March is Myeloma Action Month, and we are very excited to bring this program to you to increase awareness of multiple myeloma, as well as all those great support groups that are out there.
So at this point, I'd like go to that next slide about the audience Q&A and ask our colleague Annabel to instruct you a little bit about how you can participate and ask questions tonight. Annabel?
- Thank you, Robin. So we're so excited to have so many of you with us today, this evening, this afternoon for this webinar, a huge part of this webinar is that it's live. So our presenters are speakers are with us in the room with you, not pre-recorded. So we wanna hear from you. We wanna hear your questions when the time comes. We received so many wonderful questions, insightful questions in a response to an email that was sent. So those will be addressed at a certain point in the agenda, but as you're hearing our speakers tonight, today, please do give us those questions as they come to you. Next slide, please.
And your feedback after you're with us today is also incredibly important. It is a driving force as we move forward with this program, and thinking of the topics that are important to you, who you need to hear from, what you need to hear about. So as you close out the webinar, you will have a popup window, you can see it here. And we ask you to please hit Continue and fill out these questions. There's not many. And again, this helps us to plan for future webinars, with this feedback. And so we hope that this evening is insightful for you. And again, we look forward to hearing from you. Back to you, Robin.
- Oh, thank you so much Annabel. That's really helpful. And we look forward to everyone participating tonight. So you can see here, this is the agenda for this evening. If we could bring that agenda screen back up? And everybody take a quick look at that for the timing of this. And while you're looking at this, I'd like to tell you who we've got for our speakers tonight. First we have Dr. Kevin Brigle. Kevin is a nurse practitioner in the Hematological Malignancy Clinic at the Massey Cancer Center at Virginia Commonwealth University. For the past 20 years, Kevin's been taking care of patients with myeloma, treated on both standard therapies and on clinical trials. He's been a member of the IMF Nurse Leadership Board for the past 10 years. And next, we'll have Dr. Beth Faiman talking with you. And Beth began her career in 1994 at the Cleveland Clinic in Cleveland, Ohio, where she is employed, and immediately became involved in the care of patients and their families, living with multiple myeloma. She participated in clinical trials to approve numerous drugs to treat multiple myeloma, and remains an active member of the healthcare team in the diagnosis and management of patients with myeloma. Also a founding member of the Nurse Leadership Board in 2006. Beth is passionate about side effect prevention and management. And she's thrilled to be speaking with Dr. Brigle tonight on our call. So we will go right now into the scope of the problem, definition of side effects and impact with Dr. Brigle.
- All right, thank you, Robin, and thanks for everybody for joining us tonight. So we're gonna start this out with a slide with many of you may have seen already, and this is basically what is multiple myeloma?
And most myeloma, as it points out here, is basically no production of normal immune cells. And so they are plasma cells that have gone bad. Plasma cells are cells in your immune system that are good guys. They're the ones that give rise to antibodies. So those of you've had your COVID vaccinations, those are the ones who are gonna shoot out the antibodies to help protect you. And in real life, that's what they do. They rally and they make antibodies to any offending agent. Just like in any cancer, however, if a cell acquires enough mutations, it can go bad. And unfortunately the same thing can happen with these plasma cells. And when these plasma cells goes bad, that then becomes the multiple myeloma as it's known.
And so unfortunately, these plasma cells do when they're malignant exactly what they did in normal life. They make proteins. And so plasma cell, as it continues to grow uncontrolled, puts out more and more and more protein. And you can actually see what this would look like when we have this identified. This is an SPEP, a serum protein electrophoresis, and you put a drop of a fluid from the blood on here, and you put it to electric field, and you can see all the way down the albumin, and down at the gamma range. And that gamma range, that's the M spike that we talk about, or an M protein that's present there. And so when these proteins, what's wrong with these proteins? well, we do make a lot of 'em.
Unfortunately, they don't protect you, even though it's an antibody, they can end up clogging to kidneys. They can clog onto other organs as well and cause some problems. And the other thing about multiple myeloma is when we think about where these cells are, they're grown in that soft tissue, which you can see on the slide there, in the middle of the bone, but the myeloma cells can also interact with the hard part of the bone, and that's called the cortical part. And when they interact with a cortical part of the bone, that's when they can also cause the lytic lesions. And those lesions and fractures that many patients with myeloma present with. And so when we think about treating myeloma, we think not just of taking care of those cells where myeloma grows, but also repairing bones and repairing other organ function that may have bad.
Okay, so when we think about basically signs and symptoms, over here on the left of the myeloma cells, again, this is some of the symptoms that we see related to the myeloma. On the right, we can see some of the symptoms, perhaps related to the treatment. And you can see that they're not mutually exclusive. Myeloma itself can cause peripheral neuropathy. We see that with some of our agents as well. We see fatigue caused by peripheral neuropathy. Infections can be caused by the myeloma, and by our treatments as well. So they're not mutual mutually exclusive. Probably, the symptoms that you have early on in your disease are related to myeloma cells. And unfortunately, sometimes replace those symptoms with symptoms related to the treatments, which we're using that as well. So really the goal of treatment is to get rid of those myeloma symptoms, treat you, and keep the symptoms that you see on the right to a minimum. And we do this, not just with treating the myeloma. We think about two aspects of treating myeloma. One is the actual treatment. And the second one, we think of supportive care as well, supportive treatment. And that is taking care of some of those symptoms that we cause. You can see the peripheral neuropathy there, the diarrhea, and things like that. So treatment goes in two directions here.
On this next slide really said, well, what happens if these symptoms aren't really treated? And that's where it becomes this big circular pathway. So if we have the unnecessary pain, we have side effects infections, certainly, it can result in depression, anxiety, sleep disturbances, things like that. Certainly, a reduced quality of life gives rise to a little bit of hopelessness, unfortunately, too. And so patients are less likely to come to their therapies if they don't think they're doing as well. They miss some therapies. And then if you're missing those therapies, it's ineffective and we get more disease progression. And then what happens when we get more disease progression? Then again, we get symptoms related to not just to the problems that we're causing with the treatment, but again, symptoms related to the myeloma again as well. So the key here, again, take care of those symptoms early and prevent symptoms that are related to the treatment.
Now these next three slides relate to the various drugs that we have for multiple myeloma. When I started, and I know when I have started, there were absolutely zero approved drugs for multiple myeloma. And we currently now basically have 14 agents and eight categories. And these are the novel agents. We still have some classic agents in there as well, but these would be the novel agents that we'll talk about. And so this next three sides kind of looks at the various groupings and we'll go through these. There's a couple of Beth's gonna talk about, and I'll gloss over those.
But if we look at this first set of slides here, we look at the IMIDS. So they're in red, the thalidomide, lenalidomide, and pomalidomide, and these are the immunomodulatory agents. And if we look at side effects of those, you can say they all have a variety of different side effects. The ones, which is gonna be significant for us, which we worry about are the DVTs or Pes or the thrombotic events. And for us, the most important part of that is preventing those. And we do that with various anticoagulating agents or even aspirin for many people. From a standpoint of a patient, we teach you to recognize the signs and symptoms of thrombosis, but prevention is number one, recognizing signs and symptoms then is number two. These drugs are all oral. They do have issues with constipation and diarrhea as well, but we try to manage those. As nurses long before these drugs were developed, many years ago, nurses have been dealing with constipation and diarrhea. So we're pretty well versed in that. And we think that we can keep that under control pretty well for most patients.
The next set up here in blue are the Mibs. And these are the proteasome inhibitors that would be bortezomib, carfilzomib, and ixazomib. In terms of these particular drugs, we have oral agents, we have IV agents, we have SubQ agents. We have a whole variety of ways of giving these medications. When we think of these drugs and we think, oh, what are the side effects of these? There is a class effect? They all cause thrombocytopenia or low platelets. It's pretty predictable, and we can manage that pretty well. They have some unique side effects as well. So probably the big one we think about when we think about Velcade and or bortezomib is the peripheral neuropathy.
And because this is such a common drug, it's probably the number one cause of peripheral neuropathy in patients with multiple myeloma. Kyprolis has an issue with congestive heart failure. And so we have to watch it with patients who have early stage congestive heart failure, you can't use it in those patients. So when we think about just using those drugs, and we think about the side effects, sometimes it's these side effects, the neuropathy, congestive heart failure, which is gonna dictate which medications we can use. If we have a patient with really severe diabetic neuropathy, then we're gonna steer away from from Velcade and steer to one of the other ones, because we don't wanna worsen that. Same thing if a person has congestive heart failure, we'll probably steer away from Kyprolis because that's a side effect that could bring up some significant heart damage. So the side effects not only are something we look for and try to prevent, but they sometimes gonna guide our treatment as well.
On the next slide here is a great group of drugs or the Mabs or monoclonal antibodies. We have three such drugs, the daratumumab, elotuzumab, and isatuximab. These are wonderful drugs, and that they really have a pretty limited side effect profile for the most part. We can't see some infusion reactions with these, but we've been dealing with these infusion reactions for many, many years. And we have ways of preventing those as well. These are great drugs because your myeloma cells are sitting in your body, and your immune system thinks that they're perfect, doesn't recognize them at all. But these monoclonal antibodies actually bind to cell surface proteins on the myeloma cells, and that allows then your immune system to recognize them and clear them. So this is really our first form of immunotherapy for multiple myeloma. And these really become a real workhorse for treating multiple myeloma. I'm gonna skip over this next one, this Blenrep.
And I'm gonna go to the next one, which is a SINE compound. And SINE stands for a selective inhibitor of nuclear export. This is one of the newer drugs that we have on board. It has a pretty limited single agent activity, but when we combine it with some other drugs, it does really, really well. It has a unique mechanism of action. Side effects, which you can see here, thrombocytopenia as well. But more significant with the selinexor is the anorexia, the nausea, vomiting, diarrhea. We can keep those things under control pretty well when we're using it. And we typically we'd use this twice weekly, but now we're using it once weekly, it's become much, much easier to use that way.
Probably the most, the biggest challenge I have, and I know Beth might echo this as well, is sometimes people just don't want to eat. It's just the anorexia that's associated with that. And that's probably the most difficult aspect of this. And then I'll kind of gloss over these then as well. So the first three here, the anthracycline, the alkylating agents, these are really classic chemotherapy agents that we use in combination with some of the novel agents. The one which you see, the ALKERAN or melphalan, that is the drug that everybody uses when they get a bone marrow transplant, a stem cell transplant. So that's the chemotherapy agent, which we use there. And then moving on to the last slide in my particular group here.
So what symptoms should I look for in report? Well, anything really. We think about anything that's new or unusual. So we think anything, any changes in urination, we have bone pain, everybody's gonna have little aches and pains, but a bone pain, that's new or unusual. Swelling, and we think of swelling, not necessarily being bone pain, but that can also be a DBT. Signs of infection. The constipation, diarrhea, again, we should be able to keep that control. Fatigue is a huge one. It's a really, really big one. It can be very, very complicated. It's not just one simple thing. And that can also lead down to on the bottom left, sleeplessness, mood swings, depression, anxiety, and things like that as well. So anything that bothers you is something you should report is about the best way to put it. And then on the last slide, I would point out that we do have some great information.
This is all the International Myeloma Foundation website, but what symptoms should you look for in report? There's some great Understanding Series, and some Tip Cards, and things like that. And so there is information available here. And so, Beth, I think you're up next.
- Thank you, Dr. Brigle. That was a wonderful overview. And I will add, I'll go a little bit more in detail with some of the other side effects, but I wanted to underscore how nice this website is. And I have a couple screen clicks I'll go over for you in a little bit. This is all on the website. This is all free. You can get this for you, mailed to you, or you can download it as well.
So I think Kevin did a great job at going through some of the side effects, and we're gonna go a little bit deeper into some of them and how to fix them. So what are some of the new things we really have to worry about? Well, they were included in many ways on the table, but things that we didn't think about before. So the GI toxicity with selinexor, We'll go into low blood counts and infection. I already saw some questions in the chat about that, and I'll try to address 'em as we go along. Eye problems with steroids and the belantamab.
Peripheral neuropathy is a big question. Ixazomib, bortezomib, thalidomide, those are the biggest culprits. Although, I've seen people on long term lenalidomide who are now developing peripheral neuropathy. And so we'll talk about resetting that and rechecking into that. Blood clot risk, and many of you who are on lenalidomide, thalidomide, pomalidomide, Carfilzomib, are taking baby aspirin, or other mechanisms to prevent blood clots. And then cytokine release syndrome, that's with our newer drugs, the CART T-cell therapy.
So what was approved in the last 2020 Expo? We talked about belantamab, Sarclisa or isatuximab. And then the last two lines, and I don't know why CILTACEL is whited out here, but the last two are the ABECMA, which is the idecabtagene vicleucel. That's the anti-BCMA CAR T-cell therapy, where CAR T-cell are taken through a machine. We'll talk about that process. And then the last one, which for some reason, it's white, but it's CILTACEL CARVYKTI that was just approved last week, on February 28th, also anti-BCMA therapy. That's very effective.
So selinexor, some of the kind of the pearls that I like to talk about. When it was with its first study with the STORM trial, 26% of people that weren't responding to anything else responded to selinexor, and that's really important, but we found out that stomach was the biggest problem. Like Kevin said, folks just didn't wanna eat. What I reinforced is the importance of taking dexamethasone in the morning, taking anti-nausea medicine, take food, and then take the selinexor. A low dose of selinexor is better than no dose.
What we found in recent study is that if you combine selinexor with Velcade, then you can have much better outcomes. There are different clinical trials combining it with Pomalyst pills and other things, but how you take it's important. A lot of my patients are so used to taking their chemo pills at nighttime, like the Revlimid and the Pomalyst, that they don't realize how important taken in the morning is. So that's one of the things that we recommend, as long as some anti nausea medicine, and there's the preventing pills at the Preventing Series, you could download the important information from the IMF website.
Belantamab mafodotin, we keep talking about this BCMA, the B-Cell Maturation Antigen. Basically, it's this marker on the plasma cells that says, "I am a grownup plasma cell." And then unfortunately, those cells grow up to be cancer. We have drugs now, such as the belantamab, and the CAR T-cell therapies, and the bispecific therapies that target this BCMA. It's only on cancer cells, not healthy cells. So what we do with this one, that is what we call off-the-shelf. We can just write a prescription for it. We have to get you to an eye doctor ahead of time, give you the medicine. It goes in over one hour. We have some eyedrops that we recommend for you to take, but it's really well tolerated, and we're watching you very, very closely. One of the biggest fears is that you can have some vision changes, but that's exactly why we as providers know how to hold the dose until the symptom goes away. And we can talk more about that in the future if you'd like. Isatuximab and daratumumab, I don't need to go into great detail about these two drugs.
They target CD-38, which is a marker on the plasma cells. And we target that CD-38, and the cells die. These are monoclonal antibodies using your own immune system to fight the cancer. And the nice thing about it is really there's this little chance of infusion reactions that patients tend to do very well on these two drugs. So if you're recommended these drugs, it's very few side effects, except for some mild fatigue that one can see. Let's dive into some more details about CAR T. Everybody's, I'm getting so many emails and phone calls about CAR T-cell therapy. And I want everybody who's on this call who wants to learn about it, to hear some information from us as nurses.
So CARVYKTI, and I still don't know if that's the right way to pronounce it, is CILTACEL is what I've been calling it for years was just approved February 28th. ABECMA, about a year previous. Both of them are against that BCMA. There are some great understanding videos about CAR T-cell therapy from patients on the myeloma.org website. I'd strongly encourage you to watch these very good videos that I've watched myself. So what about the process? I have a little graphic here, just so you all can understand what one goes through. So basically, here's a patient with multiple myeloma who's had at least three prior therapies for ABECMA, or four prior therapies for CARVYKTI.
Basically, you present to this transplant center, and we wanna make sure that you understand what the process is. And it's important, by the way, to have a caregiver throughout this whole process. So what happens is, and I shouldn't have had this as a building slide, 'cause it's not building very well. I keep hitting my clicker. Consulting with a CAR T-cell or Center or myeloma specialist is very important early on because the lists are long, and the lists are changing. Once you have that CAR T-cell treatment decision stake in contact with that CAR T-cell center, make sure that they know of your ongoing interest, and make sure you have regular visits, whether it's a telehealth visit or an in person visit, to know that this is something you're still interested in. Sometimes we see people, and then we don't hear about it again. And they think that we're gonna call them, but we don't wanna bother them. So it's good to have that communication and regular visits.
So once you're a candidate, we have insurance approval. The T Cells are harvested through the Athersys machine, and the lab engineers the cells. You'll likely need a bridging therapy to keep you in remission during a four to six week period, while these cells are manufactured. Once the lab grows the en engineered T Cells into these CARs, which drive around in your bloodstream to fight the cancer, those cells are then infused and modified into the patient. It can be done inpatient or outpatient. And in this area of COVID, many of it is done inpatient. The caregiver is so important because we need the caregiver around to monitor for this side effects of the treatment. And I'll talk about it on the next slide in more detail, the cytokine release syndrome, we know how to monitor for it.
If you're in the hospital, we do these neurotoxicity checks regularly, depending on your center. It's usually about every four hours, we'll ask, "Do you know where you are? Is your vision changing?" We'll watch you walk. We'll just assess you very closely. We'll look for your oxygen saturation. We'll look for your heart rate. Even subtle clues in case there's a problem. And we know how to intervene if there's a problem. If you're an outpatient, and maybe there's a delay chance of this, we're gonna ask you in the caregiver to look for symptoms, such as nausea, vomiting, diarrhea, headache, or confusion. But again, if you go through this process, you're gonna have lots and lots of education. Hopefully you'll be like this cute little lady at the end, who's cheering because she got her CAR T-Cells successfully harvested, she got them back. And now, she's off of therapy for long period of time. So this slide just say side effects of ABECMA and CARVYKTI. But I don't, I think it's white again. And I don't know what's wrong with the fonts.
We added this in because it was FDA approved last week. It's right hot off the presses. As nurses and providers and doctors were looking for all these subtle side effects for that cytokine release syndrome. Again, we know dexamethasone is very effective at jumping in and treating that. And then there's other medications called tocilizumab. The hospital has to have enough tocilizumab or TOCI on hand to treat this side effect if you have it. Now, I'm gonna stop there. What we wanted to do was talk just very briefly about communicating side effects, and you all tuned in to hear about neuropathy, to hear about diarrhea, and to hear about some very interesting side effects.
And so at this time, I'd like to have a back to back with Dr. Brigle, and start answering some of your questions. Kevin, can I give you one neuropathy? "I've had progressively worse neuropathy in my feet for several years, and it started with some cell transplant. I'm taking as much gabapentin as I can. I started other therapies such as exercise and regenerative medicine, but I don't always get relief. What are some of the suggestions you have?" Kevin?
- Wow, you threw me the hard one first. So if we hear anything, that's right up there, fatigue, neuropathy, really big ones. And so, yeah. What I will say is neuropathy and a treatment for neuropathy is very individualized. What one person finds useful, another person may not find useful at all. And that goes for medications.
And some patients, you might try something like Cymbalta, which is ineffective in gabapentin is effective. And so sometimes it's just trying different medications and don't be shy to do that. Some people get some relief with topical things then as well. And so some things like capsaicin cream, which can be, it's really just a warm cream, and it really more or less overrides the pathway, and kind of, how do I say, just makes the bandwidth just a little too small for the neuropathy to come through. So that's another possibility.
I have patients who get benefit from acupuncture as well. So if you have the opportunity to try that, that would be another option. But what I would say is there are a lot of different things that you can try. And unfortunately, it may not work. Sometimes neuropathy is very bad. The key thing I try to point out to my patients too, is when we start on therapy, the best way to handle neuropathy is not get it. And so it is really prevention prevention. And that is a give and take between the provider and the patient, such that you have to let us know if you're having any neuropathy. We have ways of helping with that. We can do dose reductions. We can space out the time in between. Certainly giving in Velcade SubQ is much, much better than a given an IV. And the dose reductions, I like to point out too, that the dose reductions don't mean they're any less effective.
When we start out in Velcade, we started at the maximum dose that a person would tolerate, and it can get worse and worse, and worse if you don't let us know. But we can use those lower doses. They're very, very effective. And there are two nice dose reductions that we can use. And I guess the key thing there is if it gets really bad, we have to discontinue the drug, and the drug may be working. And so I'd rather give you a little dose of the drug than no drug at all.
- I agree 100%. You know, Kevin, I always share with my patients, how is neuropathy? And like you said, it's different from individual to individual. These nerves start in your spine and they can innervate into your skin organ, and cause a sensory neuropathy, those are small nerve fibers, or it can go into your muscle, and it's a large fiber neuropathy. So finding out the type of neuropathy is really important for treatment.
The other thing I like to do along those lines of finding out the neuropathy is there are so many correctable causes. Think of the diarrhea you might have with Revlimid, you're not absorbing nutrients. So I think sometimes providers forget to check for vitamin B12 deficiencies, B6 deficiencies, and also look for uncontrolled diabetes. Excessive alcohol use can be a factor as well as acquiring new conditions. Amyloidosis is a cousin to multiple myeloma, and sometimes it might not be detected at diagnosis, or it might be something that comes up later on. Working with neurologists is very important as well. EMG testing and QSART, and all these other things. So again, working with your provider is so important, and ruling out other causes that are treatable. I remember Dr. Richardson from Dana-Farber in the early 2000s, when we saw a lot of neuropathy from Revlimid, you'll remember this, Kevin, he recommended a cocktail of alpha-lipoic acid, which is FDA approved for diabetes, as well as B vitamins, which are nerve protective B6, B12. So talk with your doctors and healthcare providers about these.
Along those lines, let's talk about fatigue. Kevin, I get a lot of questions about cancer related fatigue. Studies have shown that exercise can help, but if you're just so tired from your treatment, thinking about exercise is overwhelming. But even just walking around your house, getting some fresh air, I see that it can help. American ginseng, such as Wisconsin ginseng is something that many of the palliative departments across the country recommend. There's so many ginseng products, and it has been studied in cancer related fatigue. Again, along with the neuropathy, looking for correctable causes, severe vitamin D deficiency, not getting enough nutrients, those are reasons why people can have excessive fatigue. And then talking to your healthcare provider about the doses and how you're taking the medicines. What do you think, Kevin, about fatigue? Any suggestions?
- Yeah, I think you're right. And then more like one of the statements I always get is there that I always make, is it probably just not one thing I can do? I can't do one thing. I have to walk outta here and lose your fatigue. That's it's really a constellation of things. And you even brought up motor neuropathy. Some people might confuse weakness in their legs with motor neuropathy. So it's not really a fatigue per se, but more of a muscle weakness than as well. But your point is well taken about movement. The less you do, the less you can do. And with some patients, I tell them, they just don't have the motivation to get up, and it's, well then, set an alarm clock for every two hours and another room, and get up and get it, or upstairs, something like that. But sometimes it's motivation as much as anything. And just getting, I think your point is right, getting out and doing some things can really be mentally motivating, which can really help with the physical part of the fatigue as well.
- Right, and so some of the proteasome inhibitors, we talked about Velcade causing neuropathy. I'm just screening the chat. We have so many wonderful messages. There are so many different drugs that can successfully manage the myeloma, but not cause neuropathy to be an issue. Similar classes or different classes. We had questions about demyelinating neuropathies. A lot of times I'll get consults in my clinic with somebody that has a monoclonal protein or an M protein, and they have neuropathy. So again, partnering with a neurologist, a hematology/oncology professional, and working together to find the underlying cause of this neuropathy. Sometimes it's treated based on the clone. Like you might have an IgM clone or an IgG.
We didn't, I could talk for hours on this, right, Kevin? I think an hour is not enough to go into all these questions. Note to Robin to make these longer, but I think keeping these in mind of working with the multidisciplinary team. And some very experienced nurses have some good suggestions. I'm gonna go to one more question on our page, and then we're gonna scan the chat again. We just have so many questions, I wish we could answer them all. Diarrhea, so one of my projects as a PhD was to investigate lenalidomide-related diarrhea. And I observed that patients had staying on Revlimid or lenalidomide. You might have diarrhea, but we hypothesized, this was actually a good thing. We noticed that patients that had diarrhea, there might have been an immune effect. So controlling the diarrhea is really important. I tend to recommend for functional diarrhea, a medicine called cholestyramine or Questran. It's what's called a bile acid sequester. It's a powder and you can control how little or how much you take in the mornings. Imodium is really good for some people, as well as Lomotil. Keeping yourself hydrated is super important. Kevin, what are some of the strategies that you share for neuropathy in your patients?
- For neuropathy or diarrhea?
- Oh, diarrhea. Kevin, that was quick. I was looking at the chat. I just saw neuropathy all over.
- Oh, yeah. I think the agents, which you mentioned are absolutely key. I do find a problem with many patients who they'll take an Imodium or two and they get constipated. So it becomes a back and forth. And I saw questions of that in the chatbox as well. And that can certainly be a problem. And it really is a matter of regulating what you do. I have a woman who takes 1/2 of an Imodium every other day, and that's where she regulates. And that's what she found that she does. And so it's difficult for me to tell you what to take. It really is more or less a finding out your own, titrating it to what works for you. And it may be different when you're on the medication. Let's say it's caused by the Revlimid, maybe different during those 21 days you're on, and the seven days you're off. And sometimes keeping a diary of the diarrhea. How many times, and what medicines you've taken, you can help titrate that yourself.
- Absolutely. So what are some of the things we haven't touched base on? I did see a question in the chat about infection. So one of the questions was about pneumocystis prophylaxis after stem cell transplant. Is there any hard data that we should be recommending, I call it Bactrim to protect that. I will say there was an ASH Abstract 2020 last year. At our American Society of Hematology meeting, I remember this particular abstract. The incidence was about 0.4% in newly diagnosed patients with myeloma. Now, I don't think that this group looked specifically after transplant, but that was the most recent study I can recall, where that has been looked at. So based on the low incidence, not an allo transplant, not with CAR T-cell therapy, I don't think it's something that we recommend routinely. Do you recommend a lot of pneumocystic prophylaxis, Kevin, in your clinic for your myeloma patients?
- For our patients who have undergone a stem cell transplant, this stem cell transplant team recommends six months afterwards, and that's it. You can also, if we're worried about mild suppression, which certainly a Bactrim can do that, a question's absolutely correct. Pentamidine is another option as well, either inhaled or IV, meds does not cause the problems associated with the model suppression.
- Low blood counts.
- Absolutely. I had an interesting question I saw on the chat. So thank you for putting it in there about osteonecrosis of the jaw. That's something we haven't talked about in a bit, Kevin. The International Myeloma Working Group Guidelines do recommend everybody, regardless of whether there's damage to your bone, should be on a bone strengthening agent for at least a year. And this was just updated in 2021 by Dr. Terpos and colleagues, such as Dr. Mikhael and Dr. Durie as well. Zometa is still recommended and Xgeva, especially if you have kidney problems, but we still have to underscore the importance of dental exams. And, Kevin, I'm sure we've talked about 20 years ago. We thought they were the best things since slice spread these bone strengtheners because people weren't all hunched over. They didn't have as much bone pain. And we had this rare jaw complication. Fortunately, I've seen hundreds of patients with mild to severe as osteonecrosis of the jaw, and it tends to heal itself in many cases. I still use lots of antibiotics, oral antibiotics, in collaboration with infectious disease. And we try not to do surgery or oral extractions. Again, the jaw bone gets damaged possibly from the drugs. Kevin, what are your thoughts on ONJ? Have you seen it recently?
- And yeah.
- Any words of hope?
- Yeah, unfortunately I have seen it recently, and even in patients who have had their dental exams. And so we do have a clearance form. We have every patient get a dental exam prior to starting any bone targeting agent, whether that be Zometa or denosumab. So that's really important, and that's needs to continue. So every six months you need to have those. But can it happen anyway? Absolutely. And it can be very minor or it can be significant requiring surgery and bone removal, and things like that. One of the risk factors also associated with it is smoking. And so when we have that, so another reason not to smoke is osteonecrosis of the jaw. And those drugs don't make you live longer, but they make you live better. As Beth said, we don't wanna see you hunched over. So if you're gonna be living longer with all of our new treatments, we certainly want you living quality of life too.
- Absolutely. So something else that we didn't talk about in detail that is escaping me now, but I will remember in just a second, was the taste and smell. Some taste changes can occur based on some medications. Steroids can cause a lot of gastric reflux. And so reflux is one of those things that we forget to put people on stomach protective medications. A lot of people won't complain of indigestion or those reflux where you can have the burning in the esophagus, but it happens. So taste changes. If you look at the guidelines, the first step is a drug called a proton pump inhibitor, which is the Prilosec, and those kind of drugs to block the acid production. And if it persists, then it could be in the era of COVID. We have so many people losing their taste and smell now, this was before COVID, that might not be what it is from. Other medications, again, look at your medication list and consult with your doctor or healthcare provider for suggestions. Kevin, do you hear of the loss of taste and smell? And do you think it's from anything specific, myeloma treatment related?
- Yeah, I do. If I hear it with any drug, and I dunno if you notice this too, but it's more with Revlimid than anything that people tend to have a loss of taste. And terms of the steroids, some people don't like to take pills. "I don't wanna take another pill or proton pump inhibitor." And with those patients, I'll also tell them, "Well, then just take it in the day surrounding the steroid, 'cause you're not taking the steroid all week long." So you can do that as well. That can be effective. But the loss of taste is a huge challenge for patients. And it's a matter of finding anything that you can eat that you like, and it can impact not just eating but fluid intake as well. Sometimes it just makes water taste bad. So finding something that tastes good is really the key thing. So I wish we had a magic pill.
- I know, I know.
- Yeah, the worst was zinc, but it didn't turn out also well, but yeah.
- Let's go back to talking about diet. I get so many questions to ask. What kind of food should I eat? Dr. Durie has some very valuable information on the myeloma.org website, but I'll tell you, my recommendations are a couple of things. First of all, we used to have the food pyramid. Who remembers the eat sugars and oils sparingly, and more protein, and greens, and vegetables. And now I say, eat the rainbow. They have lots of antioxidants, fruits and vegetables. For people that have diarrhea, I recommend probiotics. You might only wanna just take a little Activia a day. I don't work for the company, I promise, but it's tends to be very palatable. It's not high in costs, and it's good in nutrition.
But probiotic pills as well. There's a whole bunch of different ones. And you can talk with your healthcare provider about what one is right for you. So probiotics, eat lots of colored fruits and vegetables. But if you have too much diarrhea, certain fruits and vegetables might be a problem for you. A lot of people worry about eating sugar because they think it causes cancer cells to grow. But I don't have any hard evidence that sugar will cause your cancer to get worse. Everybody needs a little bit of sugar to live. What are some other nutritional tips that you have, Kevin, for your patients?
- Yeah, I think one of the other things, when we talk about either both diarrhea and or constipation is fiber. And so I have patients use fiber crackers, have Metamucil, and fiber works for both constipation and diarrhea. It holds onto water. And so it can help with the diarrhea, and bulk that up, and make that less liquidy. And you may hold in longer. And in terms of the constipation, it does the exact same thing, it holds onto water. And so it bulks up your stool, and can help with the constipation also. So I think that's sometimes overlooked, and people think of fiber as being something, "Well, I just get in my diet." But there are some supplements that can be very helpful as well.
- Absolutely. I saw a couple of different places on the questions that were sent in, and is in the chat as well. We haven't really addressed a lot of the psychological aspects of myeloma or smoldering myeloma. Some of you might not need to be treated yet. The anxiety and depression. There have been studies that show that anxiety is much higher against the people that don't yet need to be treated because you're worried about needing to be treated, or how long am I gonna be in remission. At my institution, and many institutions across the country, we have to screen you before each visit and ask, "Are you sad or depressed?" or, "How many days have you felt depressed in the last month?" There's whole different screening tools that the Commission on Cancer says we should use. And we should have social workers around to help intervene and link you up with psychiatric services. I do prescribe quite a bit of medications to address depression.
And I tell folks, "It's not necessarily you, it's what we are doing to you through the corticosteroids, like the dexamethasone or prednisone treatment. It's the roller coaster of getting your labs drawn, having to wait a few days for the results, and the anxiety that goes along with that." I'm gonna go to you, Kevin, but Robin is there, and I haven't asked her a few. Talk to me about your caregiver perspective, Robin, if you're not on mute anymore, I like to hear what some of your thoughts on depression and anxiety are.
- Yeah, hi, Beth. Thank you for the question. I think for caregivers, there are other side effects that caregivers need to really understand, how can I help manage, what do I need to be aware of? Because many times, depending on what that side effect is, a caregiver may notice a symptom. If their loved one is feeling and acting a little loopy or dizzy. So maybe if you could talk about some of the things that maybe caregivers can pay attention to and to watch out for, so they can make sure that they make those right phone calls.
- Yeah, for sure. Kevin, do you wanna tackle some of the triggers to look for, or do you want me to address that?
- I'd say it's just a couple things along that. Really, the caregiver does know best in many situations. Especially, I think in early days when we used to use a lot of high dose steroids, patients would come in saying, "I'm tolerating those really well." And the caregiver would be in the corner going, "No, they're not." And so the per perception of the patient, the perception of the caregiver can be very, very different. And so much like when you're hearing about your diagnosis, the caregiver hears one thing, and the patient hears another thing as well. So I do think input from both the patient and the caregiver is really, really important. And the other thing I wouldn't overlook is that, and, Robin, you maybe can talk on this too, but caregiver fatigue and caregiver depression is very high too. And so you're not just treating the patient, you're treating the family as well.
- Yeah, that's really important, Kevin. I know that sometimes we're so focused on our loved one that we're not paying attention to our own health. We've heard that old story about when you're on a plane, and that mask comes down, you really do have to put it on yourself first, so you can be okay to take care of others. So all your caregivers out there, please make sure you're getting your exams, your annual exams done. You're paying attention to your own health, and your emotional status as well, and the fatigue that comes in during the roller coaster of myeloma, right? And I was watching the chatbox too. And I saw a couple of the other questions that you might wanna touch on. And I know lots of times, Michael will wake up with leg cramps in the middle of the night. So I haven't heard the discussion on leg cramps, and what we can do for that.
- Well, I'll tell you what I do for leg cramps. So a couple of different things in the early 20, some years ago, thalidomide caused a ton of leg cramps. And we use medication called l-glutamine, which is pills or powder. I ended up doing some dissertation research using l-glutamine for the muscle cramps. Tonic water, we used to give quinine pills, but then that can affect your heart rate, but tonic water, even a quarter of a cup, I say, leave it on the nightstand. Providers can do things such as looking for magnesium and potassium levels. Again, looking at kidney health. Making sure that it's safe to recommend over-the-counter lower doses. Kevin, what are some of the great things that you like to recommend for leg cramps?
- [Dr. Brigle] Yeah.
- Other than getting up and walking around too.
- Yeah, great things. So the reality is no one knows what cause cramps beyond dehydration. So first that's one of the things I ask, are you staying hydrated? That's the big one. And then secondly, your point's well taken with the quinine, and we used to be prescribe that, but too many people had heart abnormalities, and so that was taken off the market. And the tonic water's a great idea. And it does work in a fair number of patients, but it's one of those things you have to do regularly. You can't say, "Oh, I gotta cramp. I'm gonna sit here and drink some tonic water." It's not gonna work quickly.
But if you're drinking fluids every day, drink some tonic water with that eight to 12 ounces every day. It tastes horrible, but for the most part, it can be very, very effective. And the fact that you see a lot of wives tales, like prepared mustard and vinegar, and things like that, there's a lot of those things out there for patients who have cramps, and you hear all these different things. Even putting a bar soap underneath the bed, we've heard things like this. And that's just because cramps are a challenge, not just for patients of myeloma, they're a challenge for everybody. But probably the most effective thing I really have heard is the tonic water.
- Absolutely. A couple of things from the chat. So we talked about the leg cramps, a couple quick things. So how much B12 and B6 should you be taking? I always always check baseline B6 and B12 levels. There have been studies that show that B6 toxicity, if you aren't absorbing it appropriately can cause neuropathy. B12, if it's low or in the lowish range can cause neuropathy.
And then I would treat with 1000 micrograms or one milligram per day under the tongue. If you have very severe B12 deficiency, we can give you shots. That's supposed to be in the muscle, but if you have low platelets and it's painful, I tend to use a lot less of the shots and recommend the pills. There have been studies that say the under the tongue, sublingual B12 is absorbed just fine. The diarrhea name. I'm gonna give you the shorter name is called Questran, Q-U-E-S-T-R-A-N. The story, and I don't know if this is true or not, is that it was an anti-high cholesterol medicine, and people got constipated. And so it can be used to some extent, but then it began to be studied for functional diarrhea.
Any idea, Kevin, do you know how Questran works? I just know it works. And I give people these little packets they can put in their pockets to take with them if they're having diarrhea. Yeah, I guess a bile acid binding. And so it goes in there. Yeah, it turns to concrete, I guess, when it mixes with bile. And so that's kinda how it goes. It mixes in with everything. So that's the long and the short of it.
- Right, right. We have more questions about the doses of the gabapentin. It's interesting, Kevin, I don't see where anybody's taking duloxetine or Cymbalta for their neuropathy here and then pregabalin or Lyrica. That's also a very effective drug. I use very often and many in my neurologist do now. So the gabapentin and the Lyrica are cousins. The rumor was that the Lyrica, the gabapentin was running out. So they made Lyrica, which is pregabalin. Take it a little differently. So talk to your doctor about the duloxetine or Cymbalta that Kevin mentioned, and then the Lyrica for your neuropathy.
- We have that maximum dose of the gabapentin is actually 1200 milligrams, three times daily, but that can cost some fatigue and sleepiness as well at that dose.
- Right, I will tell you that I have escalated the doses very, very high. The clinical studies have shown that lower doses can be effective, but I have some people that swear if they go below 4,000 milligrams a day, their neuropathy flares up, and I'm not arguing with them. Take your 4,000 milligrams a day. I'll monitor your kidney and liver function, as long as your insurance pays for it. Gosh, you such great questions. We haven't talked a lot about steroids. Kevin, if you started a new person on steroids, what are some of the suggestions that you have? I think we hear less of the question about steroids 'cause we're using less these days, right?
- Yeah, yeah. Fortunately, we are using less. And so if I have the opportunity to tell patients or explain the steroids to them, again, I think it's the sleepless nights and the fatigue they can be associated with the day after the steroids. So I think finding the pattern that works for you. If you see you work five days a week, and you're off Saturday, so you could take your steroids on Friday, and so you have Saturday to recover. The other part, which I encourage patients is to take their steroid in the evening. And so if you take that steroid in the morning, this is a drug which passes the blood brain barrier pretty easily. And so by the time gets ready to go to bed, if you take it in the morning, you are not gonna be sleepy, and your mind's gonna be racing, and that can be very problematic. Whereas if you take it in the evening with a meal, very often that kind of irritation and sleeplessness that you feel will be in the morning when you wake up. And so I would say line up the cars. You do take it on a Friday night, and line up the cars or wash 'em on a Saturday.
- Yeah, or the windows.
- Or the windows.
- This has been great. I will say we did have a couple people pop up that they take amitriptyline for neuropathy and that has helped. So in case you're wondering. And so that has been in there, but in the interest of time, and, gosh, this is great. We didn't talk about sleep. Nobody sleeps well. Melatonin is generally very safe for people in case you don't take it. They have the little melatonin gummies, take one, two or three, depending on what your doctor recommends. I think that could be quite helpful. This slide here, as we're winding down, tell your team, you might have an expert nurse, or pharmacist, or physical therapist you can go to. Find somebody you feel comfortable with. Don't forget to find out who to call for what problem. Is it the allied health? Is there like an LPN or a medical assistant? Or is it your primary or referral hematologist? Keep those lines open for sure.
We have tips for talking to your provider on the website. You may have seen this before. Kevin and I, as well as the Nurse Leadership Board Team, we use input from Robin and other support group leaders to find out what was important to discuss with their provider. And this tool is a three page. Actually it's a four page tool. The fourth page is just like notes that you can write on it. But it's just asks you questions. Is my treatment working? How long do you expect it to be work? What have I taken before, et cetera. I think it's a really good thing to look at. I promised you, we would navigate to the IMF Publications. You can mail order or download them. One of the problems with this kind of a format is it can glitch if I go to the website, and also the browsers look different to you or on an iPad, but go to myeloma.org, select Publications and Videos, and click on IMF Publications.
There's so many resources focusing on side effects management for you to review at your leisure. There are the Tip Cards, the Understanding Series. And the IMF has worked really, really hard to develop these patient-focused and caregiver-focused resources for you. It's past 7:30 to 7:45. I kind of just integrated all of your questions with the ones we got before. And I wish we would've had all the time in the world, but don't forget the info line is there for you. Call the info line. And I wish I would've put it on the screen. Robin, tell me. It's 800-452-CURE in the US and Canada.
- Or you can email the [email protected].
- Very good.
- Okay, real quick. It says, "Our pharmacist said not to use melatonin if being treated for myeloma. Not a good interaction." I have never heard that in my life. So I don't know. Kevin, have you heard that?
- I have not heard that.
- Okay, so maybe taking it at the same time or depending on the drugs that you're in, it might make you sleepy. That's the only thing I could think of. I would ask why they said that to you 'cause I like recommending melatonin. So I have to research that for myself. So anyhow, that's it. I'll stop talking. Robin, take it away.
- Okay. Well, we've had some really, really great questions. Everything, just about everything that I saw over in the chatbox has been addressed. I think there was one little one about, "In addition to peripheral neuropathy when trying to manage pain, I saw someone talking about using Advil," and maybe that's not such a good idea when you have myeloma. Do you wanna just quickly touch on that?
- Yeah, so the trouble with Advil and similar drugs are called NSAIDs or non-steroidal drugs, and they're cleared through the kidneys. And so if you use them in excess, that can cause kidney damage. And with patients with multiple myeloma, we are just protective of kidneys. That's one of our number one things there because we have drugs that can cause the problem, and diseases itself causes problems to kidneys. So large amounts out. Could you take the occasional ibuprofen? Sure, but this is should not be something you're doing everyday.
- Absolutely. And real quick, the warm cream that Kevin recommended for neuropathy was capsaicin, which is ground up habanero peppers, I believe, right? And that's like add a lot of arthritis creams. Correct, Kevin? The capsaicin?
- Right, yeah.
- Okay, sorry to interject.
- All right, so I think we're wrapping up. This really has been what I think as a living well with myeloma call because we're learning more and more about until we find that cure. How do we live well? And have a good quality of life? And both of you were so helpful and in your practice, as well as here with all of us, just having a live chat tonight. So if we could go to the next slide, please. So we know about the Q&A, and next slide.
Well, I'm just gonna... so this is really important, as we wrap up, the slide before that one. Is we do wanna hear from you. And so before we wrap up, we're going to have at the close of this, a little survey will pop up for you. And it's really important. We ask you to just take a couple of more minutes of your time tonight, while it's fresh in your mind, to let us know what you liked, what you didn't like. We truly build these programs on your feedback. We want them to be better. We want them to be timely for you, to help you to do well and have those key conversations with your healthcare team. So take the time to do that. If you don't do it right now and it pops up, it's also gonna be emailed to you. So you have two opportunities to let us know what you think. Next slide, please. And again, we are so grateful for our sponsors to help us to bring you these educational programs. And tonight, that is our thanks to Bristol Myers Squibb, Janssen, and Takeda Oncology. Next slide, please.
And I guess that was the last slide. So again, thanks to all of you tonight, and we wish you well. And don't forget, this is Myeloma Action Month. Go to the IMF website, myeloma.org, and check out all the fun ways you can help, take action, and increase awareness of multiple myeloma. So thank you so much for a wonderful presentation. Dr. Brigle and Dr. Faiman, you are just angels here for all of us. So thank you for all you do.
- Thanks, Robin.
- Thank you, Robin. And don't forget to call the myeloma infoline if you didn't hear your question answered. We had hundreds of questions. We did our best, I promise. Or the call, the infoline or [email protected], I believe. Right, Robin?
- Yes, and that number for the infoline is 1-800-452-2873, which is CURE. It's a great number.
- Thank you. Have a great night or day.
- Thanks, everyone.
The IMF thanks the following event sponsors for their generous support:
Bristol Myers Squibb, Janssen, and Takeda Oncology