Symptom Management in Multiple Myeloma: Practical Tips for Patients and Families

 Donna Catamero:
I'm Donna Catamero. I'm nurse practitioner out from... I think New York City is the sister city to LA but on the East coast. And I'm going to be talking to you today about, we got a lot of pieces over the past two days and how we can put them all together. So hopefully tying a nice bow to this great weekend. So I'm going to be discussing myeloma basics, newly diagnosed relapse, living well, and symptom management. And I know Dr. J gave a wonderful myeloma 101. He spent 45 minutes, and I'm going to try to accomplish the same thing in two minutes.

So myeloma is cancer of the plasma cell. Plasma cells live in our bone marrow. They produce our antibodies, which are types of proteins, and they're really a major force in our immune system. What happens in myeloma is that these proteins or antibodies, we have several of them, IgG, D, E, A, et cetera. Myeloma, the plasma cells overproduce one with the reciprocal suppression of all the other antibodies, and this overproduction of this antibody is non-functioning. So off the bat, these patients are immunocompromised.
So with the diagnosis [inaudible 00:01:15] myeloma, your immune system isn't working maybe as well as my immune system. And so these plasma cells, these myeloma cells are now in the bone marrow and they're crowding out. So we said yesterday that the bone marrow is the factory. It produces our white cells, our red cells, our platelets, or red, white and rosé wines. And so usually one of the first symptoms is fatigue, which is caused by the anemia because the bone marrow is too crowded out to produce these red cells and these cells, these plasma cells also with this abnormal protein, can affect our kidneys.

So I often think too when I'm washing my hair, and then I notice there's water pooling around my ankles, that that protein gets stuck, and it clogs... it damages the kidneys. So that's how I kind of look at it. So we have altered immune function, anemia, renal insufficiency, or renal dysfunction. But then also these plasma cells are sending signals to cells that break down bone to accelerate it while our cells that make bone can't keep up with the cells that are breaking down the bone.

And the end result is about 90% of patients at some point in their disease course will have lytic lesion, pathological fractures, or bone thinning. And can't stress this enough, infection. So, again, off the bat with the diagnosis of myeloma, our immune system is not functioning the way it should be. So the leading cause of death with myeloma patients is infection. So we have to be very vigilant when it comes to infections. So you need to know the signs and symptoms of what an infection looks like.

So any type of fever, 100.4 or higher, that is right away, you're calling your healthcare team, and keep other signs. So you might not present with a fever. Could be dizziness, short of breath, cough. I don't care how many phone calls I get in a day, any signs and symptoms of infection warrants a visit. And then we really focus on prevention. So hygiene, good hygiene. They did a recent test in New York City. I don't know why they did this because it makes my commute terrible, but they swabbed the New York City subway.
Why would they do that? And so they found the Bubonic plague. I don't want to know that. But then I'm not going to hold onto the rail and then grab a handful of M&Ms and throw them in my mouth. So hygiene, hand washing, right, it's the best prevention. And then environmental control. So I want to know what's going around in my area. Is flu and COVID, is that on the incline? Am I going to be in a crowded room such as this? Don't... And I'm going to take precautions.

So when I'm out flying and I'm in an enclosed space, I'm okay putting a mask on, and you should feel the same. So look at your environment and be the best judge. And then, there's things that I can do to help prevent infection. So I'm going to say this multiple times throughout my presentation, immunizations, vaccines. And sadly, lately, vaccines it shouldn't be politicized. They prevent infection. Thank you. Thank you. So, seasonal flu... seasonal COVID, RSV, they're giving us protection, and that said... we said leading cause of death is infection.

I want to give you something to prevent infection. So, making sure you get your seasonal flu, be up-to-date with your pneumonia vaccines. And then I'm probably looking at your treatment, seeing if you're at higher risk for infections, and I might add in some supportive care to again give you that even more extra protection. We talked about the kidneys. So how do we protect your kidneys? So biting myeloma. So the treatment you're getting is helping that protein from building up and affecting your kidneys.

Hydration. Two liters a day. And this is not counting coffee, so we should try to get our hydration in. NSAIDs like Advil, Aleve, we all love them. But I would say just open up that medicine cabinet and just get rid of them. I had a patient who went on a skiing trip, took some Advil. The next Monday, her kidney function was in the trash. So just get rid of it. If you're in pain and need medication, call me. We can discuss a good pain regimen for you. And then IV contrast for CT scans. Sometimes it's unavoidable.

So if you do need IV contrast, I'm going to give you some hydration afterwards to again flush out your kidneys. And then just be alert. Monitor, do I have really foamy urine? That could be some excess protein. Might not urinating enough. Keep these things. This is the things that you want to monitor and report. Bone health. So again, the treatment I give you for your myeloma is going to treat your bones. Good nutrition, vitamins. So we should be checking our vitamin D levels. Everyone in New York City is vitamin D deficient because we all stay indoors. We have long winters.

So just vitamin D is important because it pulls the calcium and brings it back to the bone. And so we also include calcium supplementation. That's something you do want to check with your team if you can... if you're a right candidate to take calcium as well. And then we heard yesterday about exercise, and that really is great for the bones. So I avoid the gym like the plague, but walking is really a great form of exercises. I'm the one who's like, "Oh, it's only 10 miles away, we can walk." So walking is great.

Pain. This really impacts our quality of life. Sources of pain, bone disease, fractures, lesions, neuropathy, which I'm going to discuss a little bit later on. And then our medical procedures, because who doesn't enjoy a good bone marrow biopsy? So prevention. Your team, a lot of part of your supportive care. So you have your treatment for myeloma, and then you have supportive care that we give you. We give you bone strengtheners to really solidify the bones to prevent pathological fractures.

And then medical procedures. I try to combine everything at once. So if you're going in the room, get everything done. No one should be a martyr for pain. If you're in pain, talk to us. We can put you on a pain regimen. If it's localized to an area, radiation may be a good option. And then surgery. So, kyphoplasty where, if your vertebrae, because of bone disease collapses, we can go in there, put some cement in. And so, sometimes surgical procedures can help as well.

And then again, activity. Physical therapy. I often send off my patients with the script for physical therapy, and I think that can also help with neuropathies as well. So now I want to switch gears and start talking about some of the therapies we give for newly diagnosed treatment. Some of the symptoms we see associated with newly diagnosed treatment. So, newly diagnosed treatments new diagnosed consists of three phases. Induction, which is the goal of reducing the disease burden. Consolidation, which is to really... the goal is to eradicate any remaining myeloma.

And then maintenance. So lower intensity, but I'm going to try to delay myeloma from coming back. And so what standard of care is now evolving? Most of you might've been on a three-drug regimen. And so now the landscape is changing so that we include a four-drug regimen. This consists of a monoclonal antibody, so Darzalex, Sarclisa, proteasome inhibitor, Velcade or Kyprolis. And then a modulatory agent, which is going to be Revlimid and a steroid. And as I said, we're also going to add in some supportive care medications.
Medications like Velcade and Kyprolis can put you at higher risk for shingles. So we usually prescribe Acyclovir. Aspirin to prevent clots. Revlimid, Pomalyst, they put patients at higher risk for clots. So we want to try to prevent that. And then again, as I said, the bone-strengthening agents. So everyone's favorite, steroids. It's usually the backbone of a lot of our therapies, not just newly diagnosed, and it has... and I think most of this, the side effects, are really steroid-driven, and it affects everything.

Mood swings, which I've... irritability, which I've had to be the brunt of. Dexamethasone can cause cataracts. So if you're on a steroid as part of your regimen, don't forget your annual eye exams. Can cause muscle weakness. Sleeping disturbances. That's a big one for patients. And then heart burn, sugar levels. It really does run the gamut. So sometimes when we have the regimen, take this in the morning. You might be less tired at night, but some patients actually like dosing at night because

by the time the steroid kicks in, it's the morning.
So see what works best for you. Take that steroid with food because it can really disrupt the stomach. And then steroids can also weaken the immune system. It's kind of like you're damned if you do, you're damned if you don't. So we might add in some extra protection for infection. Peripheral neuropathy is another big one, and this is a little more difficult to manage. Some of the treatments we give for myeloma... Sorry. Some of the treatments we give for myeloma, such as Velcade, can cause neuropathy.

And this is like numbness, tingling hands, feet, and it can progress go up the leg. And this is something I try to avoid because it is fairly difficult to manage. So we've tried to look at how we're dosing the Velcade. At our institution, we do weekly administration. Velcade used to be an IV formulation. Now it's an injection, and we saw a reduction in the peripheral neuropathy. Sometimes it's helpful for supplements, but before I would add in any vitamin B supplements, I would see if you have any deficiencies before we add that in.
And then you want to make sure you're creating a safe environment because if you're not... your sensation is diminished in your feet, you don't want to trip on rugs or get burned in the shower. There are some things that I can give that can maybe help, but again, I don't have a silver bullet, but things like Gabapentin, Cymbalta, Lyrica may be helpful. Physical therapy is something I often recommend too for patients, but this is fairly challenging to manage, and that's why I want to prevent it.

And if you start having these symptoms, it's very important to report them right away because I might want to change how I'm managing your myeloma. Blood clots can put patients at risk for DVTs and PEs, and some of the treatment regimens we give puts you at higher risk. So baby aspirin is usually for someone with normal risk, but patients with other comorbidities or maybe less mobile could be at higher risk for developing a clot. So maybe you need more than a baby aspirin. Maybe you need a DOAC like Eliquis.

And then there's other strategies. So I love those compression socks. I always wear them when I travel on a plane. That can be very helpful. Moving, mobility, walking. And then, if you're traveling, if you're going to be in a long car ride or a flight that's more than two hours, you want to discuss that with your provider because maybe you're going to need something temporarily to help prevent a blood clot. So if I have a patient who's on a six-hour flight, I might give them something like a Lovenox to provide them some extra protection while they're traveling.

Stem cell transplant. So yes, we're still doing stem cell transplants for the time being. And I look at this as being three phases. So eligibility. So, usually the eligibility for a transplant is age, but that's a gray area because New York City, we have five centers of excellence. So if your are cut off at Mount Sinai is usually around 70, 72, then maybe if you walk 10 blocks in another direction, their eligibility criteria might be a little bit different. But insurance sometimes dictates that.

So if you are a stem cell transplant candidate, we collect your stem cells typically after four to six cycles of your induction therapy. And then you'll be ready for your transplant, which consists of high-dose chemotherapy, which is Melphalan, and it's pretty intense. So patients do get some GI symptoms. They'll lose their hair. And it's typically in an inpatient hospital setting, though there are some institutions that do transplant as an outpatient, but in my institution, it's an inpatient admission.

They're there for about two weeks, and then we're sending them home to recover. But we're going to keep a close tab on these patients because their blood counts have dropped, and we're going to make sure if I have patients who need transfusions or need a growth factor support, I'm making sure I provide that. And then patients are going to spend the next hundred days recovering, getting their stamina back. And then around day 100, we're going to restage you. So we're going to do the bone marrow biopsies and blood tests and see how well did this transplant work, and hopefully, our goal is to get patients in a complete remission.

So, part of this transplant process, we do see a lot of GI symptoms, so constipation, and I do also see some diarrhea with the induction phase. And this could be due to some of the opioids we give, some of the supplements. So again, hydration is key, but a bowel regimen is also helpful. Increasing fiber can help with the constipation. But if you're having constipation, there's medications that we can use to get you back on track. Anorexia, which is because you lose the desire to eat, which is very common when patients are getting that high-dose chemotherapy in the hospital for two weeks.

And it's rare that I don't see patients that have not lost weight from their transplant. So usually patients do lose a few pounds from their transplant, but that recovery period, that while they're home, is to really gain back some of that weight. So we work with our nutritionists to make sure that patients are getting high-protein, high-calorie diets during that time. And then diarrhea, which is maybe more common in the maintenance phase. And usually, I see it's associated sometimes with fast foods. So again, having a bowel regimen of hydration and things like Imodium can be very helpful.

So now I'm going to move into the relapse setting and then managing these symptoms. So I don't know if you've ever been to a myeloma talk. This graph is always somehow snuck into a presentation. And I want to say this is a little outdated historically. So one of the defining characteristics of myeloma is its relapsing nature. So you get into a remission, you stay in our remission, but the myeloma creeps up again. And historically, we said your first line of treatment, you get the deepest and longest remission.

But then eventually the myeloma comes back, and we give you your second line of treatment, but you might not respond as deeply or as long, and then eventually the disease gets worse and worse. This is historically because now we're seeing patients who've had 10 prior lines of therapy who are getting into a deeper and longer remission than they ever had with their first line of therapy. So times are changing. This is a little outdated, which I'm finally happy to say. And there's many options in that relapse setting.

We have many classes of drugs, including the new kids on the block, which CAR T therapies, bispecific therapies, monoclonal antibodies, et cetera. And then we can combine... mix and match and combine them, though we have over 40 combination therapies that we can offer patients. We have belantamab mafodotin here, and I'm very optimistic that hopefully by the end of the year we'll add another drug in class to our toolbox. And then always stressing too, because my specialty is clinical trials and research. Clinical trial is offered to you. That's something that you can consider as well.

So I want to talk about, again, the new kids on the block. They might live in different houses, but they have a very similar mechanism of action. We're activating that T-cell to attack the myeloma cell. So in CAR T therapy, I'm taking your own T-cells, genetically re-engineering them with like a GPS so that when they get infused back into you, they know exactly where to go and attack that myeloma cell. But this is a process, and this is not something that I decide you're getting CAR T, next week, you're getting CAR T. This is a process.
So we collect your T-cells, we then take your T-cells, ship them off to be manufactured, and that can take anywhere from four to eight weeks. During that time, I'd want to have... make sure that you have disease control. So I need to give you something called bridging therapy to really keep your disease at bay until those cells are ready. Once those cells are ready and arrived at my site, I'm going to bring you back in for some additional chemotherapy. And the purpose of this chemotherapy is to kill off your T-cells, which is going to room for your new CAR T-cells that I'm going to infuse.

And this CAR T infusion again typically takes place as an inpatient, but more and more institutions are doing this as an outpatient. But we're going to monitor you for some unique side effects. So novel therapies equals unique side effects. And then bispecific T-cell engagers, similar mechanism [inaudible 00:21:14] taking that T-cell and bringing it to the myeloma cell. But now I'm using an antibody that's going in, it's grabbing onto that T-cell, grabbing onto that myeloma cell, and bringing the T-cell in very close proximity to the myeloma cell, and then the T-cell sees it, kills it.

So it's like holding hands and bringing them together. And this is off the shelf. So if I think I want to start... you want a bispecific, I can start you the following week. So this is very don't have to wait for manufacturing. And so we're very, very fortunate that we have four available agents to us. Three of them target BCMA, and then we have Talquetamab or Talvey that targets GPRC5D, and the more are still under clinical investigation targeting different antigens on that myeloma cell.

So bispecific CAR T's, again, similar mechanism of action. So similar side effect profile, and you've probably heard cytokine release syndrome, which is common in both therapies. And this is when we have a large bulk release of these proteins that kind of go... your immune system is going haywire, and it can affect every organ system. The most common side effect of cytokine release is a fever, and then it can progress to low blood pressure, low oxygen levels. But in my experience, majority of patients are going to get that low-grade fever, and that's when our little spidey senses go up, and I'm going to intervene.

So first sign of a fever, I'm giving the antidote, the tocilizumab, and patients are doing well within the next 24 hours. So patients have described it to me as, "You know how you get your flu shot. You get achy, you have a low-grade fever." This is... can be what a mild form of CRS feels like. And then we have the neurotoxicity ICANS. And this is going to happen during the first two weeks of therapy, where patients can complain of headache, confusion of even seeing hallucinations. And this is very rare, but it can happen, and it's important to know about it.

And this is why care partners are so important, because in CAR T, this can be a little bit delayed and patients might already be home. So this is something that we really need a care partner if we're going to do this. So how do we try to mitigate some of these side effects? So with cytokine release and CAR T, we're giving bridging therapy because we want to decrease the bulk of the disease. We see that when we do that, we have less neurotoxicity. With bispecifics, we give step-up doses. So little dose. Second dose is a little bit more, and then we get to the full dose.

By doing this, we decrease the CRS. But we have our antidote, tocilizumab, that we give when we do start seeing signs of CRS. For neurotoxicity, we manage that slightly difference. We often give corticosteroids, but the thing to really take home is that these symptoms are self-limiting, manageable, and patients tend to do very well with both these therapies. But infections. Both these CAR T's and bispecifics, three of our bispecifics target BCMA, our current two CAR T's target BCMA, and we find that this increases the infection rate by a lot, and we see even severe infections.

So infections leading to IV antibiotics or a hospitalization. So anytime anyone is on a BCMA targeting agent, I'm doing more prophylaxis. So I'm initiating something called IVIG because we see with BCMA targeting drugs, the healthy IgG levels plummet. So I'm going to supplement patients with IVIG, I'm giving them antibiotic prophylaxis and again vaccinations, making sure patients are up-to-date. Of course, we're going to keep the shingles prophylaxis on board. And then I'm going to monitor blood counts. So remember that t-shirt, "I love neutrophils?"

If your neutrophils drop below a certain number, I'm going to give you injections to boost that up. And then we see with our GPRC targeting bispecific, some on-target off-tumor side effects, and some of these are GI symptoms. So we do see the alterations in taste, the anorexia, the weight loss, which is opposite of things like dexamethasone. So I want to talk about some of these oral side effects. So, especially with the Talquetamab or Talvey, we are seeing a higher incidence of dry mouth, taste changes, difficulty swallowing, which all equal weight loss, and that's what I don't want to happen.

So with dry mouth, saliva substitutes can be very helpful. Taste changes, a little more challenging to manage, and taste changes just like neuropathy greatly affect someone's quality of life because I love food, and it's really not just loving food, but it's also a social interaction. You're going out to dinner, you're with friends and family. So this really can affect someone's quality of life as well. And I don't have something that I can give that will erase the taste changes. So we do things, the benefit may be helpful, but it doesn't get erased at all.

We are using dexamethasone mouthwashes. We're using things like citrus candies to try to stimulate the taste, but I really... I incorporate my nutritionist early on in these therapies to work with our patients to come up with a meal plan to supplement certain tastes. If I'm lost my sweet tooth, but I still have the sense of savory, what can I do to add into my meal plan that can enhance some of the taste? So work very closely with my nutritionist. We also tell our patients good dental care because that can help with some of the dry mouth and the difficulty swallowing.

Again, [inaudible 00:27:59] difficulty swallowing might mean diet modifications. Patients will tell me that, "Eating meat like steak is very difficult to swallow. So we're going to have to change some of the things we eat" and monitor the weight because, again, with these therapies are very, very effective. The majority of patients do respond to these therapies, but I don't want patients to lose weight. If that's the case, that might be a dose change, or maybe I need to dial back the frequency. So we do see some skin side effects.
So with bispecifics as a class, we can see generalized body rashes depending on how big the rashes. If it's localized, we can do topical steroids. If they're generalized, then we might need some oral steroids. With Talquetamab, again, we're going to see the on-target, off-tumor. So GPRC is on the cell surface of the myeloma cell, but it's also on keratinized cells, which is the tongue. So that's why we get the oral mouth toxicities, but also on the skin and nails.

So we can see peeling on the palms and the soles of the feet. We can see dry skin. So with the dry skin initiation of this type of therapy, we want the heavy barrier creams. If I see hand-foot peeling, I'm going to add in ammonia lactate lotion. And then we can see these nail changes. So, unfortunately, patients will have these nail changes for the duration of their treatment. The other skin side effects once we manage them, but the nails are slow growing, and patients will have these nail changes, and usually it's brittle, ridging nails.
We often will tell patients to use those nail hardeners. Polybalm is another good supplement for patients to help strengthen your nails and keep those cuticles short and clean. Any signs of infection will put an antibiotic ointment around the cuticles. And then finally, I want to end with living well. So fatigue. So basically everyone has it, and it's not just symptoms of the disease or the treatments I give, but also emotional stress, I think, causes fatigue. So you add this all together, I think we're all walking around a little tired.

But you see here in bold, again, I'm going to go back to yesterday's talk about activity. So physical activity. Even when it's hard to get off the couch, once you're moving, you actually start feeling better. But we also see that a third of patients complain of anxiety, quarter of patients report depression. And I actually think this is very underreported. Patients still feel like this is a taboo that they don't want to talk about. But if you don't tell us, we can't help you. We have resources. Let us know. We can provide that lending hand. So please talk to your team. There are support groups.

There's IMF. We can get you through this. So please don't feel that you can't report these symptoms to us. And then sometimes we have tunnel vision. Myeloma is the biggest problem in our lives right now, but then we forget everything else. So don't forget about your primary care doctors. And don't forget about all your other screenings. So your colonoscopies, your mammograms, prostate cancer screening, skin screening. We can't forget about those. And try to live the healthiest lifestyle that you can. If you're smoking, stop it.

And then stress reduction. I don't know. I can't recommend that I still struggle with myself, but if things get too much for you, just take a break. And then our care partners, because they're so essential. And we talked about how they're important for our CAR T therapies or bispecific therapies, and we see that studies show that having a strong social network improves outcomes. Having that person there in the exam room is a second set of ears. And we know that studies show you need to hear something three times before you can really commit it to memory.

So, really, having someone there to support you. When you're overwhelmed, sometimes you're not hearing things. And so having, again, that second set of ears and eyes can be very helpful to our care and outcomes. But then we also need to care for our care partners. Sometimes I walk in an exam room like you're the patient, but the care partner looks worse. So we have to care for our caregivers. They're under so much stress. So please, same thing, stress reduction. Really take time for yourself and don't forget about your needs and your care as well.

And we have resources for you at the IMF to help support you through this journey. And again, we have these pamphlets. They're available online. They're available to be mailed to you. We have them outside. Our website is full of information, videos, and you're here right now, so you're putting this together. And this is my last slide. I want to thank you. I'm a small cog in a big machine. I'm with 20 other nurses on the leadership board. And really, our goal is to really advance the care of patients. So with that, thank you so much, and I think I have some time for questions.