Multiple Myeloma Podcast

Addressing Comorbidities in Multiple Myeloma: Treating People, Not the Disease

Joseph Mikhael, MD; Ashley Rosko, MD


June 02, 2022

This transcript has been edited for clarity.

Joseph Mikhael, MD: Hello. I'm Dr Joseph Mikhael, and welcome to Medscape InDiscussion on multiple myeloma. Today we're talking about addressing comorbidities in multiple myeloma. I picked this topic because it's so critical in the field of oncology in general, but in particular in multiple myeloma, where over half of our patients are aged 70 years or older. Historically, as myeloma treaters, we haven't been ideal in fully assessing our patients and understanding their needs and their comorbidities, and then appropriately responding exactly as how to manage their treatment. In fact, very often we've thought of it as just deciding, is this patient transplant-eligible — yes or no? As we're going to hear today, it's a lot more than just that. If we're going to give ideal care to our patients, we need to understand this topic much more fully.

It is absolutely my pleasure to have not only a world expert in myeloma and oncogeriatrics but also a very good friend of mine, Dr Ashley Rosko, with us today. She is an associate professor in the Division of Hematology and she's the medical director of oncogeriatrics at the Ohio State University. Welcome. Ashley, it's really great to see you.

Ashley Rosko, MD: Thank you, Joe. I'm very pleased to be here today.

Mikhael: Let me kick us off with a case that may trigger some of the discussion. A 71-year-old woman who has diabetes and hypertension and had a myocardial infarction (MI) 4 years ago was just diagnosed with multiple myeloma. The community oncologist is wrestling with whether or not this person should go to transplant. In my introduction, I noted that historically, it's really just been a flow chart that has two options: Are you to transplant or not to transplant? That is the question. Hopefully one of the key lessons today is that this isn't the only question. It's one of many questions, but nonetheless, that's what's happening in this case.

Why don't I turn it over to you and say, what is your initial approach to this? What are you going to do with this patient to better understand their fitness and frailty going forward?

Rosko: This case illustrates the majority of patients who are coming to our clinic diagnosed with multiple myeloma. The average age of a patient diagnosed with multiple myeloma is 70 years. When you think about comorbidities, more than half of our patients diagnosed with multiple myeloma have at least one comorbidity. But it is increasingly common. You see many comorbidities, and understanding the severity of those comorbidities plays a good role here. We're very good at understanding what medical conditions they have. It’s important to be able to characterize treatment strategies, whether it's transplant or nontransplant. I'll just take a moment to mention, I'm very pleased that the field of myeloma is moving away from that stratification and moving away from up-front deciding whether a person is eligible or ineligible for therapies. Our clinical trials are moving that way, and as a field we are moving away from this kind of up-front stratification.

But it gets back to that question about when someone is coming into your clinic and they are multiplying therapies for patients with newly diagnosed myeloma, how do you design treatment for those patients? In myeloma, specifically in the field, a lot of work has been done in this area to be able to characterize frailty. Frailty is a term that is used more frequently than it is defined. We have many scales that have been validated in the field to be able to identify risk for morbidity, risk for mortality, risk for treatment or drug discontinuation. These scales can help guide us to estimate what the patient's underlying health status is.

I'll take a moment to review some of the skills that have probably been most rigorously defined. Not to say that because the skills that we have available, each one has its own barriers to use. Each scale has its own deficits. But at least we are talking more about moving away from chronological age alone and getting to the sense that underlying health status or fitness on one end, or frailty, is a way for us to be able to better estimate patients' health, better estimate treatment tolerance, and better estimate transplant eligibility.

Those scales are things like International Myeloma Working Group frailty scores, the revised Myeloma Comorbidity Index, or even the Simplified Frailty Scale. Each of these scales moves beyond chronological age alone and adds additional health factors that can better estimate treatment tolerance.

Mikhael: Can I interrupt for just a quick sec on that notion? Because I think something that historically we've always used as the key barrier or the key factor was the age of the patient. I'm very encouraged to see that we're moving beyond that. Even just a couple of years ago, we published the first ASCO guidelines in myeloma, and we said that age alone should not be what is defining a patient's transplant eligibility or treatment eligibility. I wanted to emphasize that point as you're going through, because historically geriatric assessment, as it were, is just looking at the date of birth. And clearly, the date of birth means something, if I'm hearing you correctly, but it's not everything. So these scales that you're about to describe are taking us beyond that single date.

Rosko: To your point in that sentiment, there probably are so many questions where people ask or query, what's your average age cutoff for a transplant? We don't have one. We don't have one at our institution. As part of our guidelines, many institutions are moving away from age-based transplant eligibility, because you can't tell me that there's a biological difference between someone who's 70 or 71 and really have a good sense of what is going on to that patient's health.

For patients with multiple myeloma, health status is dynamic, and a new diagnosis of multiple myeloma can significantly affect your underlying health status — whether that's your function because of pain related to myeloma bone disease, whether it's related to being fatigued and tired due to anemia, or just having a new diagnosis of cancer. When you treat a patient newly diagnosed with multiple myeloma, their performance status will improve because health-related quality of life tracks with disease control. If you can get disease control, knowing where you start may not be where you end. Understanding that this is a dynamic process is really the definition of frailty. It does change with the time of diagnosis; it does change with therapy. To that sentiment of saying it's not age-based, but also understanding that as someone is diagnosed with myeloma and gets better disease control, their functional status can significantly improve.

Mikhael: That's really helpful. Let's talk a bit more about these tools, these scales, because there are so many of them, and a lot of people say, "Look, can you just simplify it for me? Is there a 3-second bedside test where I can wave some magic pixie dust and know what the core properties are and the frailty index of this patient?" I know that's impossible, of course, but tell us how you use these tools in your clinic. What would be the best tool to use for our community oncologists and myeloma treaters listening to this?

Rosko: I don't think it's so far off. There are ways that we are doing this in practice that we can operationalize it further. For example, the International Myeloma Working Group scale looks at things such as age, activities of daily living (ADLs), instrumental activities of daily living, and comorbidities. In the real world, how we break that down is by asking, "What are you able to do at home? Are you doing the grocery shopping? Are you able to cook meals?" That can give you a good sense of their ADLs, right? Those are things that you're asking when a patient is coming into your clinic.

One of the important things that I do in focusing on aging adults with multiple myeloma is not so much to ask about what activities they are doing, but also to ask what they have stopped doing. It makes a big difference if someone is doing all of their activities of daily living but previously used to run 3 miles a day and have stopped doing that and can't do that any longer. That's a bigger difference in terms of being able to get about your house vs stopping doing much more physical, intense activity. Asking what patients are doing in terms of activity and also asking what they have stopped doing are things to be able to gauge their underlying health status and is in alignment with those types of frailty score calculators.

The revised Myeloma Comorbidity Index is a little bit more detailed. It takes in things like age and performance status but also incorporates what we would consider the gold standard for frailty assessment, which is the Fried frailty phenotype. Definitely those type of skills, I would say, are more research-centric and are not necessarily things that are routinely employed in a routine clinic. But it's also asking to get a sense of what their underlying function is more objectively. Asking things about the ability to get up and walk, and timing that, and getting objective measures of health is a great place to see where the field is going. There are many more scores; there are many more calculators. But the idea of characterizing fitness or frailty using a tool is better than using age alone. We have much more robust measures to do that, using things such as a comprehensive geriatric assessment, where we go through the domains of underlying health status and can do that in concert with routine oncology care.

Mikhael: That's fantastic. I'm learning a lot here today. One of the key things you're sharing with us is asking patients both what they can do and what perhaps they've stopped doing, and then to close the loop on these tools.

Before we move on to thinking about specific comorbidities of interest, it's important for us to together think a little bit about, what does this mean at the end of the day? What's the point here? Historically it's always been, are you transplant-eligible or not? It's really been that simple pathway. From what I'm hearing from you and from what I've seen you work on and publish, it's not just being transplant-eligible or not, although that's part of it. It's also deciding what is the best regimen for patients, and what is the best dosing within that regimen? And then having this ongoing assessment, once you've established that baseline, so that we can make adjustments and patients can remain on therapy. And having an ongoing assessment of their quality of life, so that we're not impairing it so much that they're ultimately just going to discontinue therapy. I know I may be putting words in your mouth, but is that is that the endgame here? It's not just to transplant or not. It's also to assess what the best regimen is and what's the dosing of that regimen, and then the ongoing follow-up through that regimen.

Rosko: Joe, your point there — talking about right-sizing therapy for patients and making sure that patients are able to receive and continue on treatment — is really the goal. If you provide someone with a very intensive regimen up front and they're already sick because of their multiple myeloma diagnosis, and then you're intensifying their therapy, it's a mismatch. And then therapy is held, therapy is discontinued, and you have these big, long treatment breaks. That really does a disadvantage to an aging adult with myeloma. So right-sizing therapy and being able to maintain patients on the therapy that they need is pivotal.

Mikhael: Let's think about a few comorbidities that I know have particular interest. I'd like to focus on two of them — neuropathy and cardiovascular issues — because I know those come up so much.

Rosko: We talk about neuropathy and we talk about cardiovascular disease because especially in a patient who is newly diagnosed with myeloma, we have that chance, that window, to prevent problems.

An example of this kind of preventive approach is someone who comes in and you already see that they have diabetes and are on several neuropathic agents; that's an opportunity to for us to say, let's not make things worse for you. If someone has preexisting neuropathic conditions, we have options, right? We have studies on that. For example, the ENDURANCE study looked at frontline VRd vs frontline KRd and found no differences for patients who are standard risk. But at the same time, there are certainly options to say, "If someone comes in and we know even in those studies that there was more neuropathy in a bortezomib-based group," then we have an opportunity to say, "Well, let's try to use an alternative agent with less neuropathic symptoms to not exacerbate symptoms in someone who already has a preexisting condition." So those are the cases where we say, "There are data to say this one's better than that."

But are you harming someone [with therapy] and causing more neuropathic symptoms, falls, and immobility, or is it just a decline in their function? That is a type of preventive approach when it comes to neuropathic agents. We're well-attuned and well-engaged to be able to quickly come off of doing twice-a-week therapy to once-a-week therapy. I'm curious to know your opinion a bit about this. What are your thoughts on once-weekly vs twice-weekly therapy in someone who is otherwise fit?

Mikhael: I generally always use bortezomib subcutaneously weekly. Both of those strategies reduce the neuropathy and even reduce the thrombocytopenia. I give it twice-weekly very rarely, even just for the first cycle. As you said, if someone has very intense active disease, we want to try and bring it down, especially in the context of renal insufficiency.

The other point I'd like to make here is how important it is to have that ongoing assessment. Because at the first sign, even grade 1 neuropathy, it's critical to intervene by reducing the frequency of the agent and maybe having to discontinue it. We never want our patients to go down a one-way street of neuropathy.

In regard to cardiovascular issues, what are your insights there?

Rosko: When we're looking at drugs that include carfilzomib, these composite measures in many of the studies look at cardiac impairment, shortness of breath, and hypertension. We see this more commonly in patients who have carfilzomib. If someone has active cardiovascular disease or has had a recent cardiac event, then I would be more thoughtful about using that agent. But for someone well-controlled who has a history of coronary artery disease — a remote history, like this patient you describe here, having an MI — it doesn't necessarily preclude me from using that drug. That's important to know.

Some people have asked whether you do baseline echocardiography if you're worried. I am definitely much more in tune to the symptoms related to carfilzomib, such as shortness of breath and the new development of high blood pressure. But I don't want to preclude a drug that is very effective for patients in the relapsed setting or, in many cases, in the frontline setting, too. So I want to be clear about that. I am saying that I'm thoughtful about those toxicities, but it doesn't necessarily mean I don't use that drug.

Mikhael: I'm completely with you there, and I've written a little bit on this. The only situation where tomorrow I wouldn't give carfilzomib to a patient would be if they, have at that very moment, uncontrolled hypertension or uncontrolled heart failure. What I would do is delay it — not necessarily discontinue it, but delay it until that was under better control.

I have to take advantage of the fact that I have the medical director of oncogeriatrics from the Ohio State University here. I want to ask you, Ashley, there are so many aging issues that can influence us. I always say, "I don't treat myeloma; I treat people." Sometimes we can get so focused on the plasma cell, we lose the rest of it. Do you have some pearls for our audience today around polypharmacy or other issues?

Rosko: One of the challenges in treating aging adults is needing this additional expertise. Many institutions have the ability to partner very closely with geriatricians in their field, and geriatric oncologists are a much-needed necessity. But here at Ohio State, necessity is the mother of invention. One of the things that we really needed was to be able to help not only older adults with multiple myeloma, but older adults with cancer as a whole. So, one of the things that we created was a multidisciplinary clinic specifically for aging adults, which unites allied health professionals to do a comprehensive geriatric assessment as the standard of care. Many key stakeholders of leading agencies have recommended that all patients aged 65 years and older diagnosed with cancer undergo a geriatric assessment, which is a comprehensive, in-depth evaluation of a patient's health status, with a concerted plan for that patient. So I created and developed a clinic for older adults that has such health professionals as a pharmacist, a nurse who is trained to do an in-depth cognitive assessment, physical therapists, case managers, and an audiologist. And we work in concert to be able to address the needs of aging adults with cancer.

Mikhael: That's fantastic. I commend you on that. I know we're going to learn a lot from you and from what the outcomes of that clinic are.

Before we wrap up, Ashley, what's one thing you want to pass on to the listeners that might be useful?

Rosko: Myeloma is a disease of aging adults, and shifting away from away from age-based decisions is really important. Thinking comprehensively about your patient and being able to start a myeloma therapy, and understanding that frailty is dynamic and reassessing a patient at the time of their diagnosis and throughout their treatment course, really improve treatment tolerance and health-related quality of life.

Mikhael: You've heard it from one of the world experts in the field, Dr Ashley Rosko. Thank you so much for joining me today. There has been so much to take out of this — that age alone clearly is not enough as we address comorbidities in our patients and recognize how common these comorbidities are, how they dynamically change even with response to their therapy, and that there are validated tools and validated models for assessment, as we've heard of this clinic that can really help patients along. As I mentioned earlier, we don't treat myeloma; we treat people. It's so critical that we capture this as we go through. Thank you again for your time with us today, Dr Rosko. Thank you to our listeners; we trust this is helpful to you as you care for your patients.

Rosko: Thank you.


Multiple Myeloma

International Myeloma Working Group Frailty Score Calculator

R-MCI: Myeloma Comorbidity Index

A Simplified Frailty Scale Predicts Outcomes in Transplant-Ineligible Patients With Newly Diagnosed Multiple Myeloma Treated in the FIRST (MM-020) Trial

Treatment of Multiple Myeloma: ASCO and CCO Joint Clinical Practice Guideline

Frailty in Older Adults: Evidence for a Phenotype

Comprehensive Geriatric Assessment

Carfilzomib or Bortezomib in Combination With Lenalidomide and Dexamethasone for Patients With Newly Diagnosed Multiple Myeloma Without Intention for Immediate Autologous Stem-Cell Transplantation (ENDURANCE): A Multicentre, Open-Label, Phase 3, Randomised, Controlled Trial

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