Case 1: A Patient With Symptomatic Multiple Myeloma

Beth Faiman, CNP, PhD, Cleveland Clinic, Ohio, walks the audience through the decision-making process for treating a patient with symptomatic multiple myeloma who relapsed through multiple lines of therapy.

Transcript:

Beth Faiman: Thank you for joining me at this Oncology Learning Network activity titled Treatment Decision-Making in Relapsed or Refractory Multiple Myeloma. This is a peer-to-peer discussion and my name is Beth Faiman. I am a nurse practitioner from the Cleveland Clinic in Cleveland, Ohio.

What we're going to do tonight is we're going to go over some case studies. I think it's so confusing what to do and when to do it when you're managing patients with myeloma. Not only the diagnosis, but what's the right best first therapy, what's the best second-line therapy and subsequently. So, we're just going to go through that right now. When you look at a patient with relapsed/refractory multiple myeloma, what does that look like?

First of all, how do you diagnose myeloma? Multiple myeloma is a cancer of the bone marrow plasma cells. The plasma cells are responsible for protecting you from getting sick, making these immunoglobulins. And unfortunately, at some point these immunoglobulin proteins over accumulate in the bone marrow and the proteins spill into one's peripheral blood.

This leads to these hallmark symptoms of CRAB: hypercalcemia, as there's damage to the bones and then that spills the calcium into the blood; renal insufficiency, that's an elevated serum creatinine level which can occur; anemia, and that's based on the overaccumulation of plasma cells in the bone marrow space, and then a hemoglobin of less than 10 is hallmark for that; and then bone damage.

So, if you have this CRAB criteria, you have a patient with myeloma. If you're watching this and you don't see a lot of myeloma patients, think about anybody with renal insufficiency, anemia, hypercalcemia, bone disease, as being a candidate for ruling out a myeloma diagnosis.

Let's say you diagnose somebody with multiple myeloma, you gave them A, B, or C induction therapy, and we have so many new gold standard induction therapies available right now, at the time of this recording. We had 2 FDA approved therapies with 4 drug regimens with a CD38 backbone that were approved this year in 2024.

And at any rate, that patient gets a good induction therapy and then they relapse. So what does that relapse look like? There's two typical kinds of relapse. The first is a biochemical relapse. That's where a patient goes into remission and then the proteins kind of creep up, but they don't have any symptoms of the disease. You tell the patients that their labs are worsening or changing and they say, I feel great. We'll talk about that through our case studies.

The other pocket is the clinical relapse. That's where patients have that CRAB. Again, the aggressiveness of the disease, the hypercalcemia, renal insufficiency. Do they have a doubling of the M protein? Is the LDH increasing? And so then you have a decision point to make.

Okay, so if you have a patient that has an increasing protein, do you monitor them every 1 month, 2 months, 3 months, or when do you change therapy? And we'll talk about that in a moment. If you have a symptomatic aggressive relapse, that patient needs to change therapy emergently. And fortunately as of 2024, there are many therapeutic options.

Let's dive into case 1. One of the things I'd like you to consider as you're watching this is what kind of lines of therapy do you have experience with and what factors influence your treatment decisions most often? I started managing myeloma in the early 2000s. I've been in my same role at the Cleveland Clinic for over 20 years as a nurse practitioner, and I'm so fortunate to see all of these different lines of therapy and how they've changed over time. So I'd like you to think about what you see in your practice and what kind of lines of therapy you have experience with and what factors influence your treatment decision-making such as fitness, frailty, or other.

Let's talk about a patient with symptomatic multiple myeloma. So what does that look like? So I discussed how one presents with myeloma. Now there's this slim CRAB. I talked about the CRAB, the hypercalcemia, renal dysfunction, anemia, and bone disease, that's CRAB. But as of 2014, the International Myeloma Working Group had criteria for diagnosis of myeloma that included the slim.

So you might have somebody without CRAB that has just 60% clonal bone marrow plasma cells in their bone marrow environment. They might have an elevated light chain ratio of greater than a hundred or a difference in light chain or there might be an MRI or radiographic evidence of lytic bone disease, they might not have any symptoms though.

This particular patient presented to the ER, just not feeling well. Very, very sick, throwing up. Getting to the ER, they were diagnosed with hypercalcemia. Serum calcium level was 18, normal is about 10.5. They also had renal dysfunction. The creatinine was over 3.0. That occurred probably from the hypercalcemia and maybe dehydrated from that calcium salt elevation. They also had anemia.

They were referred to a specialist and a FISH panel was obtained, which had a deletion of 13q and translocation of 14;16 and a gain of 1q. The cytogenetics were normal fortunately, but that LDH was elevated and when you look at the revised staging for the International Staging System for multiple myeloma diagnosis, an elevated LDH of any kind will be more of a high-risk disease. Their stage was 3 based on the hypercalcemia and renal insufficiency. So unfortunately, the higher the stage--and there's 3 stages of myeloma--that contends a poor prognosis. They were then diagnosed with lambda light chain myeloma because they were referred to this amazing advanced practitioner.

The nurse practitioner ordered all these great labs. By the time they got hydrated, the calcium came down to 10.2, but the beta-2 macroglobulin, which is a nonspecific marker of inflammation in the body, that was 5.3 milligrams per deciliter. We talked about the LDH being 289. Creatinine after hydration came down to 1.6, hemoglobin 10.8, the lambda-free serum, and this is important, there's a lambda-urine and kappa-urine light chain, which is very... it's inaccurate. We want to check with the serum test. So the kappa-lambda light chain in the serum is what you want to look for. This is a test by the light-chain binding site.

The year 2004 was the first time we had a test. This is interesting because when I started practicing myeloma, we called these people non-secretory because we didn't have this test. So those were our non-secretors. Now we can actually say they're secretory.

And so the lambda-free light chain in this patient was 1832 with a normal being 19.4 and a urine M spike of 2.72 grams per 24 hours. Bone marrow aspirin biopsy was obtained and it had 80% clonal lambda-free light chain restricted cells.

What did this patient get? Well, they had renal insufficiency at diagnosis. With the hydration, it came down to a little safer range. Standard of care at that community institution was 2 drugs, oral lenalidomide and oral dexamethasone. They received that therapy for about a year, decided "I don't want to go through a stem cell transplant."

A standard of care is typically an induction regimen and then if you're transplant-eligible, you get a consolidation with the high dose of melphalan and a stem cell transplant and then a maintenance. And so that's pretty much in 2024, a recommended standard of care. Again, we use a lot of shared decision-making when we talk about this, what are the patient preferences? And this is a perfect example of how this individual was transplant-eligible but was too busy caring for a sick spouse and couldn't take the time away for the transplant.

So they had a remission, but then they progressed and they went to the line of therapy 2, which is elotuzumab. This is an anti-SLAMF7 monoclonal antibody with pomalidomide and dexamethasone. Not quite a home run. They only had a short remission. Again, probably due to the fact that this was a high-risk disease. The line of therapy was daratumumab, carfilzomib and dexamethasone in February of 2023 to July of 2023. As you can see, these are short remissions. We expect somebody with myeloma to have a nice longer remission.

Based on the relapsing nature of the disease and based on the indication at the time, ciltacabtagene autoleucel or cilta-cel, which is a CAR-T cellular therapy--notice that this patient didn't get a transplant but they were able to still get CAR-T--was given to this patient in August of 2023. Unfortunately, probably because of the aggressiveness of the nature, the patient did not have a response and the labs were increasing. And you can see the urine M spike at 4 grams for 24 hours. Lambda-free light chain at 2812. So still also transfusion-dependent with their anemia.

So I'd like you to think this is now line 5 of therapy. Patient was started on talquetamab. They had all these effective therapies, or should have been effective therapies, but now unfortunately they're progressing, but they started talquetamab.

What is talquetamab? Talquetamab is a bispecific antibody. It targets a GPRC5D receptor on the cell, which is expressed on keratinized cells. So, an innocent bystander. When you're giving talquetamab, which again is a very effective bispecific antibody, the innocent bystanders, the keratinized cells that express GPRC5D will be affected. So you see a lot of oral and skin toxicities with this. And you also can see planter palmar desquamation. They can have sloughing of the skin on their hands and their feet and then you can also see some weight loss. The taste just changes and I think for a lot of people that's the most frustrating part about talquetamab is that they want to have a piece of pizza and it doesn't taste like pizza, it tastes like cardboard. So you have a lot of those taste changes that can occur.

So for this patient who progressed who hadn't been in a good remission, still stayed on quarterly zoledronic acid because they had a lot of bone disease and a lot of skeletal fractures, we gave them antibiotics and antivirals. What do the bispecific antibodies do? It's really targeting the T cells and they're engaging the T cells to become fighters. The T cells and the B cells are all important in immunity. And so we do see a lot of opportunistic infections.

So we place patients in my institution and many other institutions across the country on prophylactic antibiotics, primarily Bactrim is the one that we use a lot of for PJP prophylaxis. If you have neutropenia like our patient did here, maybe a levofloxacin for the neutrophils less than 500, and then antiviral therapies such as acyclovir or valacyclovir.

The taste changes can be very devastating to some people. Olanzapine is something we use to encourage appetite. It can in some patients, again anecdotal, a lot of this we're working on these studies to see what works, what doesn't work. But a lot of it is patient-dependent. I use a lot of olanzapine at bedtime. It not only helps them sleep, but it can actually help their appetite. I started 2.5 milligrams going up to 5 or 7.5 as needed.

Dexamethasone rinses is controversial. There are some patients in the early MonumenTAL studies that use dexamethasone rinses. I find it very helpful for some people, especially when they get a little inflammation and some people can get some mouth sores. We have magic mouthwash we use at my institution, which has Benadryl, maalox, and lidocaine, as well as some dexamethasone in it. And for some people they find that very helpful.

The serum IgG level will go low. Patients will have this functional hypogammaglobulinemia and an absolute hypogammaglobulinemia and the serum IgG level will be low. This patient had a light chain type of a myeloma and so the normal immunoglobulins are not being produced because there's overproduction of that light chain. So you're going to see that really high. And these patients will need IVIG to keep that IgG level higher. The NCCN guidelines support that as well as some of the other guidelines that are in existence.

For the nail and oral side effects, we talked about the dexamethasone and olanzapine for oral. The nail peeling can be kind of annoying for patients. I recommend putting nail hardener and keeping their nails really short. Some people will walk in and they'll have band-aids taped around their nails because it pulls on their clothing and that could be annoying. But the fortunate part in my experience, and I've given a lot of talquetamab, once the nails fall off, then actually it's just growing back and it's less bothersome. Some people have real good success though by just keeping the nail hardeners on.

For the skin toxicity, you can get these weird rashes. So I use cortisone cream, sometimes some Benadryl as well to help the sleep. And if there's an itching component, non-sedating antihistamines during the day. I had a patient come in not long ago and she says, "I'm having this horrible rash, it's a side effect of my medication, I need to stop the medication." She was a nurse and when you get a rash from a drug, you need to stop that medication. I said, no, don't stop it. That's your immune system being activated. I recommended some of the aggressive lotioning. Aveeno is a good lotion that some people really like in my experience. And then we also recommended the antihistamines and it's pretty self-limiting usually within the first month. And she had an amazing response to therapy so she was happy to stay on that.

Jenny Lamberts: Beth, can you talk about what that patient's outcome was after switching to talquetamab?

Beth Faiman: The outcome after the talquetamab... They had an amazing response to therapy. What's interesting is that in olden times with myeloma, there's this old graph from the International Myeloma Foundation that talks about that most patients are diagnosed with this MGUS, a precursor to myeloma, and then there's a time from 0 to 40 months or 40 years even where they don't even have symptoms, they don't need treatment. But then once they need treatment, the remissions and relapses get shorter.

But what's really neat about this drug and similar drugs is you can have your deepest remission, so you can have a good response. After we saw this patient had 2 months remission here, 2 months remission there, they're coming in weekly for the shots. A drug like talquetamab where it's given subcutaneously every other week. They don't have to worry about taking pills at home every day except for the preventative medications. So a nice deep response.

They had what was called a VGPR decreased by 90% by the International Myeloma Foundation criteria after the first month and they achieved a complete response. So the Lambda light chains became normal, actually low, and then the Kappa light chain low. But then you need the supportive care to protection against the infection.

Jenny Lamberts: Sure, that's wonderful.

Beth Faiman: Thank you. So it's really so exciting to see that once you find, I tell people it's like the right recipe to treat your myeloma. I like to cook and bake and so it's about finding the right recipe. You are an individual and we have all these clinical studies that support the use of these drugs. We know that efficacy, we know the safety, we know pretty well by the time they're approved, the supportive care.

And a lot of it is that discussion with the patients, encouraging them to stay on the therapy that we know is likely working and then showing them the labs. So what I do on a daily basis when they come in to see me, I go over the labs, what was this number, what you start with and what is the number now? And we have some graphs in our future case study as well.

Jenny Lamberts: And you've talked a little bit about this, but what adverse events of talquetamab do patients think about the most and how do you use shared decision making to talk them through some of those aspects?

Beth Faiman: Yeah, absolutely. The patients, by the time we are recommending talquetamab, it's the fourth line of therapy. So they've had to have had a lot of therapies. So sometimes that discussion is, I'm not in remission. This is a good drug. I'll take whatever you're recommending at this point.

But for some people they say, okay, there's 2 bispecific antibodies that are FDA approved, well two classes. The one is the BCMA-directed by specific antibody, that's teclistamab and elranatamab. Those are both at this time FDA approved. And then the GPRC5D is the talquetamab. We selected talquetamab for this patient because they already had cilta-cel, which is a BCMA-directed CAR-T. And there's emerging evidence that says it might not be the best idea to go right from a BCMA, if you didn't have a response, class switch, go to a different class of drugs. And so that's kind of what we discuss.

A lot of times, again, it's that we don't want to make it paternalistic but you don't want to scare them when you look at the side effects. I think a lot of it is reassurance and that's where the multidisciplinary team does a good job. A lot of times it's the doctor that says, this is what I think is best for you. And then the advanced practice provider, pharmacist, nurse go in as the supportive role and say this is what we're recommending and this is what you need to do.

One of the things we like to recommend is that they have a caregiver or somebody to talk with. Two sets of ears. We write things out, again pieces of paper, like look for this side effect and if you have this, do that. This is when you call us. So making sure that they're protected as best as they can I think is super important.

Jenny Lamberts: Wonderful. And my next question would be, you talked about the patient's care team. So what role specifically does the advanced practice provider play in that care team responsibility when you're having those discussions?

Beth Faiman: Yeah, so that's an excellent question and I think the big deal is that it changes per institution, per state. So there's different practice patterns in each state. So I practice very differently as an AP who's been in the current role for over 20 years managing patients. So I have a whole group of patients that this is a patient that I saw and I said, you know what? You already had CAR T and it didn't work very well. I think this is the next best thing for you based on how fast the disease was progressing. They didn't have time to go on a clinical trial. They didn't want to have the clinical trial responsibility.

And what's so nice is that these drugs are to be given in the community. So we could start this person at our hospital and then 90 minutes away where they live, they can get this drug. So not only is it different in that I was the one that said, I think this is right. And then I talked with the doctor and said, this is what I think. And we came at that decision together. But just having that team approach.

Sometimes I'll bring in family members on FaceTime that might live in Atlanta or Texas or another state to help them with it conversation so they don't have to be physically there anymore. That's what I think COVID taught all of us is you don't have to have somebody physically there. But again, having that discussion and then being able to say, Hey, we know how to manage these side effects. We're going to get you ramped up in the hospital for a short stay. But then once you're safe, once the acute side effects are done, and we can talk about those too as well. We can get you into your community where you don't have to drive to see me all the time and then we can do video calls to touch base and I can work with your local care team.

Jenny Lamberts: That's perfect. And that's where patients want to be. So that's wonderful.

Beth Faiman: Yes, of course. I always tell the same story people, we have Lorna Doone cookies in our hospital and patients love these little shortbread cookies. Half the time people have never heard of them. But we're very fortunate, we have a patient fund where they can get their cookies, they can get snacks, they can get a cup of soup if they want, they have art therapy. And there's this whole experience at a lot of hospitals, not just my hospital. There's a lot of this experience for people that don't get out much because they're worried about infections. They're possibly a little older and they're not working anymore. This is a safe space coming to a hospital and it's experience.

So if it's every other week, sometimes they decide that they want to make the drive and resources are an important thing to talk with patients about because no matter where you are across the country, many of the pharmaceutical companies have amazing reimbursement programs as well as the local charities like The American Cancer Society and The Leukemia & Lymphoma Society.

If you want to get a second opinion at a center or we saw how quickly from 2022 to 2024 this patient just blew through a bunch of therapies, maybe they would've been able to have a clinical trial and gotten access to talquetamab early on and haven't gone through those relapses and such. So anyhow, there's a lot of supportive care that goes on with it.

And I think the original question 20 minutes ago when you asked me is what's the role of the team? It's varied, but everybody has a very important role that is enacted in this discussion. I have some great pharmacists that work with me. And so when they're admitted, because when you get this drug, you have to be at most institutions admitted for a short hospital stay to protect against top 3 things. One is cytokine release syndrome, which is just killing all the cells really fast and they can get a high fever and some other symptoms, which we know how to manage. You can also get an ICANS, immune cell effector neurotoxicity syndrome, which you can get a little confused.

But these are things that we know how to prevent, we know how to treat. And we do it mostly in either a hospital environment or for some centers it's a very closely monitored outpatient environment. And so talking patients through that initial course knowing that when they're discharged, the chance of these things happening is very low, then it will be something that they're more likely to feel comfortable taking.

Jenny Lamberts: Wonderful. Thank you.