Case 2: A Patient With Multi-Relapsed Multiple Myeloma

Beth Faiman, CNP, PhD, Cleveland Clinic, Ohio, discusses another case of relapsed/refractory multiple myeloma and explains the treatment decision-making process through multiple lines of therapy.

Transcript:

Beth Faiman: Let's dive into another case study. Why don't we? This is a patient who was diagnosed with multiple myeloma and they had the CRAB type of features where they had a little bit of anemia, the hemoglobin was less than 10, and they did have bone disease. It was one of those situations where they had a lot of back pain, they went through physical therapy, and the back pain wasn't getting better. They had really no other symptoms other than the back pain.

Then all of a sudden they got an MRI because of the worsening back pain and the x-ray didn't show anything. The MRI had T4, T6, T12 thoracic vertebrae had lytic lesions as well as L1, L4 and L5. So lots of disease.

And that's an important teaching point because when we have patients with myeloma, skeletal survey used to be the gold standard of care in diagnosing these patients. We would get x-rays and then say, okay, x-rays are fine, they don't have any bone involvement and now we know that you're going to miss 30 to 40% of osteolytic lesions and why wait until you're having pain with these symptoms and diagnosing them earlier.

So the International Myeloma working group has guidelines for the detection of bone disease and those are from the 2019 Hillengass guidelines with the IMWG that say we should be getting a whole-body PET/CT scan, if that's what the insurance will pay for, or a whole-body low-dose CAT scan.

Now the billing of that is a little tricky in some centers. PET/CT is actually a little bit easier, but some payers will reimburse better for a spine MRI, so you can get that skeletal x-ray if that's right for you. But imaging the spine is really a good area to look for. And that's what was done here.

Didn't have any antecedent plasma cell dyscrasia. They didn't have MGUS that they knew of ahead of time. The LDH was low though and the stage was 1. They just had this bone disease and were diagnosed with IgG Kappa symptomatic multiple myeloma based on those lytic lesions.

And this is interesting because I don't think I pointed out to you that this patient was diagnosed actually in 2014. So IgG Kappa tends to be a little bit better prognosis, more commonly diagnosed than just the Lambda light chain, Kappa light chain, or IGA, and they tend to do better.

So you can see the labs here, the IgG was 3850. Normal is about 1400 depending on your lab. The serum M spike was 2.98 grams per deciliter. Serum-free light chains were also increased. The Kappa was 334, not sky-high though. They did have measurable protein in the urine over a gram for 24 hours. Urine albumin was low though, which is great. That urinary albumin is a really important thing to look at because it looks at how much tubular damage you have to the kidneys. And so they didn't also have a lot of bone marrow plasma cell infiltration, only 30%, but they met criteria for the diagnosis of myeloma based on the osteolytic lesions that were identified in the spine.

So in 2014, a very common standard of care, especially in the community centers, including my academic center, was lenalidomide and dexamethasone. Patients were started on this oral regimen that was FDA approved for relapsed myeloma in 2005. Eventually had an FDA approval later on and very well tolerated. The idea here was sequencing in 2014.

We had carfilzomib for relapsed myeloma, but we didn't have elotuzumab, we didn't have daratumumab, we didn't have ixazomib, we didn't have a lot of the drugs that we have available to us today. So there was a lot of the sequencing going on. So anyhow, unfortunately this patient had a bad outcome with this one month of therapy. They had a fever, grade 4 neutropenia, probably again the dose might've been a little high. Who knows why this person had such a side effect. But they did go into acute renal failure after starting the lenalidomide and dexamethasone.

So the doctor's like, Nope, we're not doing this anymore. We're going to go to the next line of therapy. So bortezomib 1.3 mg/m2 was given from 2003 to 2010 pretty regularly as an IV days 1, 4, 8, and 11 was the standard of care. But it did lead to a lot of peripheral sensory neuropathy, eventually some motor neuropathy. That usually occurs between 4 to 6 months of therapy.

Around 2015 we were starting to give weekly subquetaneous lower dose with weekly dexamethasone, which patients tolerated quite a bit better. And this individual was on it until 2016 when they had progressive disease. Mild peripheral neuropathy wasn't terrible.

So in 2016, what did we have? Ixazomib was available. We said, okay, well maybe they started on lenalidomide 25 mgs. It might've been too much. The disease was still kind of active, so let's give lenalidomide another shot. Ixazomib 3 mgs weekly, days 1, 8, and 15 with one week off. Lenalidomide at home, pills. Again, days 1 through 21 Q28 days. And then weekly dexamethasone was started in August 2016 until 2017 when they progressed for progressive disease.

And they started daratumumab. Daratumumab, bortezomib, dexamethasone based on the CASTOR regimen was every other week. Bortezomib eventually due to the sensory neuropathy. Daratumumab was the standard schedule. Back then we were giving it IV. It was before the Faspro, which we give subq. Back in the day, it was weekly for 8 weeks, starting week 9 to 24, you go every other week and then you go monthly. But unfortunately stopped the bortezomib due to the neuropathy, but that was okay because they did great on single-agent daratumumab.

We ended up getting rid of the dexamethasone. That's when we started peeling away the dexamethasone is as an anti-IL6. It's very effective at poisoning the myeloma cells, but we just find with these effective therapies you just don't need as much. So they discontinued this after 3 years.

And I mentioned in the first case study, if you were there to listen, what's neat about myeloma these days is finding the right treatment. You can have longer remissions. It used to be shorter remissions and relapses, and then eventually they progress.

So here's a graph that shows the history of the last few years of therapy and you can see the ups and downs nature, but then unfortunately these clones changed. And the reason we do ongoing in myeloma is to suppress malignant clones. There's this concept that was mentioned by Keats in 2011/2012 of clonal evolution. When you have a dominant clone in the bone marrow space that drives the production of the myeloma protein, causes that diagnosis of myeloma, and then they go in remission, it leaves space for another clone to emerge.

We did some mapping, that second, third, fourth clone will look nothing like the initial dominant clone. In myeloma, even 2024, the idea of continued suppression of those malignant clones so that the other clones can emerge is kind of what we do. And I explain to patients it's weed and feed on the bone marrow, so you're trying to give a little bit of extra drug, whatever the maintenance or the continued therapy to suppress those clones so that the healthy cells can grow. So it's not too much that healthy cells can't grow in the garden, but the cancer cells cannot.

And you can see here at the disease progression, how high the light chain was, unfortunately. That was a serologic disease progression. No new bone disease at that time. In 2022 they were given line of therapy 6 now, elotuzumab, pomalidomide, and dexamethasone. They were able to stay on that for almost 2 years, which is amazing because daratumumab is an anti-CD38 monoclonal antibody, highly effective. But there's a lot of discussion as to whether or not elotuzumab, the anti-SLAMF7 monoclonal antibody can be just as effective sequencing.

And so in our experience, especially if somebody has this biochemical disease progression, especially if they're a little more frail, we still will offer elotuzumab, that option. And this person was primarily treated in the community and came to us for a second opinion in this situation.

Line of therapy 7. Wow, lots of therapies. We had a baseline, Kappa free serum was 1067. And that's an important teaching point too. Patient had a dominant M spike at diagnosis over 2 grams, 30% Kappa light chains in the marrow. And what happens over time is the clones change. So they no longer had a high M spike, but the free light chains were increasing.

So when you're looking at patients with myeloma and you're following their disease trajectory, make sure you're checking the free light chain serum as well as checking the intact M spike. And you can see the talquetamab started here when the disease was up and they had a nice response.

Jenny Lamberts: Knowing what you know now about this particular patient case and going through those 7 lines of treatment, would you have approached this case differently in hindsight?

Beth Faiman: Yeah, I mean absolutely. We don't give any of the drugs in myeloma 2024 now the way they were approved, for example, daratumumab was an IV. We were giving it only in heavily pretreated myeloma. And now just about everybody gets daratumumab upfront. It's very effective therapy, very well-tolerated and it has very little toxicities. And so patients can do very well for a long time with this.

We talked about the bortezomib used to be IV and twice weekly. Now we know a lower dose can carry a lot better. I think one of the challenges is that this patient was treated in the community, they again didn't want an upfront transplant for many reasons and it just didn't work out for them. A lot of the fear of what does a transplant entail, not wanting to go to a larger institution for a second opinion.

And I think that this is where I tell anybody who's watching this, early referrals and collaboration of care. Some of these drugs might be a little challenging to give but once you give 1, 2, 3 people these drugs, even if you don't manage myeloma very often. These are pretty well-tolerated and easy to give and establishing that network, so referring to the institution, getting a collaboration, then you learn who to call, when to call. I have nurse practitioner and physician phone numbers from all over my little area in Pennsylvania and West Virginia and Michigan and New York, and they know to call me.

And so that's priceless because these drugs were meant to be given in the community and as a referral center, we want to give the patients back. So we don't want to keep the patients, we want to make sure that we address all your needs when you're referring them. But we want to give the patients back.

And it might be as easy as maybe you don't feel comfortable giving talquetamab or a similar drug, but there's lots of supportive care. You can get IVIG locally, you can get zoledronic acid locally, they can do labs locally and then I can do virtual visits to touch base or we can have them come for the talquetamab or other as there are some toxicities that need to be addressed.

But again, that collaboration of care needs to start early and the patient needs to know that it's okay. Because one of the biggest problems I hear is that they don't want to hurt the feelings of their local doctor by thinking that they don't know what they're talking about. And I said, that's not it. I know people at academic centers that actually aren't very confident. Just because you work at a large hospital doesn't mean you know everything. So that collaboration of care is super important and bringing the patient and the whole healthcare team in I think is important.

Jenny Lamberts: And I think you bring up a really great point, which is that what would you say to a community-based advanced practice provider who is maybe hesitant to send their patients to a large academic center because they have a relationship with that individual and they don't want to lose them as a patient. What tips would you give that person?

Beth Faiman: We love your patient, but we want them to be with you. We want you to have your patient. We are a referral center. We are very busy and we want to make space for the next person to come in.

So again, that relationship building is so important for the institution and I know there's a hesitancy and not knowing who to contact and when. So I think it's on us as the referral center to be like this is what we do, we refer and we recommend treatment, but bringing them into the discussion as well.

So I recently had a situation a couple of weeks ago where I had a patient that came from another state that they had heard from their support group about these drugs and they were really hesitant to come up, but they were able to secure funding to come for that second opinion through their insurance company. They didn't even know that their insurance company would pay for travel to a referral center, but they do. I heard Walmart has a good program, a lot of people do.

But anyhow, when they were in the office, I said, so these are some options that I would give you. Let's call your provider. So I literally called the office on the phone. I said, who do you call when you need to call them? And they gave me the nurse's number. The nurse got the doctor who I'd never talked to and I talked with the doctor. We discussed the case together. So bringing them into the decision making I think is also a very wise way of building relationships. And again, setting the understanding that you are good at what you do, you just might not have as much experience in this area. And that's where I'm here to help you and my team's here to help you.

Jenny Lamberts: It sounds like that direct communication on both sides is really, really important.

Beth Faiman: I'm so glad you picked the right words to say what that was, picking up the phone and calling. But that direct communication I think is really challenging when we're all busy finding people in the clinic. But I'm more than happy to step away, as are many of my colleagues, to take a phone call from a referring provider and it can be a nurse practitioner, physician assistant, doesn't have to be an MD. Anybody who's managing the care of that patient to have that discussion about what's best for that patient. Because they know the patient better than I do. I just met them and maybe I only saw them twice.

And so maybe this other clinical trial might be not right for them. But this talquetamab, we can set you up with the pharmaceutical company. We can have them come in, set you up for the REMS, the risk evaluation mitigation strategy program so that you can know how to give it. Everybody's educated, we get you the drug, we tell you how to give it, and really you only need a couple of doses under your belt before you feel a lot more comfortable and then you end up getting a process in place.

That's the other thing, sharing our processes of how we get these up and running and what we do. I think then you don't have to send them to me. Maybe this is your first person we work together with and then the subsequent ones you get to start.