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Real-World Treatment Strategies for Older Adults with Multiple Myeloma: A Conversation with Dr Larysa Sanchez
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Released: August 26, 2026

Joshua Richter
Joshua Richter, MD

Real-World Treatment Strategies for Older Adults With Multiple Myeloma: A Conversation with Dr Larysa Sanchez

[00:00:04] Joshua Richter, MD: Welcome to Hematology Highlights, brought to you by Decera Clinical Insights. I'm your host, Dr Joshua Richter from Mount Sinai.

In our previous episodes of the series on relapsed and refractory multiple myeloma, we've discussed bridging therapy and strategies for patients who are ineligible or decline T-cell-redirecting therapies. Today, I want to bring it home and talk about real-world data, including what to expect and the patient experience.

Now, myeloma is most commonly diagnosed in older patients, so I really want to drill down on the experience and the needs for older individuals with relapsed and refractory multiple myeloma. For this discussion, I'm really honored to be joined by my colleague, Dr Larysa Sanchez, assistant professor of medicine at the Icahn School of Medicine at Mount Sinai and the director of geriatrics and myeloma at the Center of Excellence in Multiple Myeloma. Larysa.

[00:00:57] Larysa Sanchez, MD: Thanks so much, Dr Richter. Happy to be here and to discuss this really important topic today.

[00:01:02] Joshua Richter, MD: Let's dive into the big picture. When you meet an older patient with relapsed/refractory myeloma for the first time, what are you actually assessing beyond the disease status itself? What does a real geriatric evaluation look like in your clinic, and how does it change the decisions that you make?

[00:01:20] Larysa Sanchez, MD: So, I think this is, you know, an extremely important thing to consider for older adults. So, when we think about geriatric assessment, it's really made up of a number of components. And the five most important components to me that I really look at are comorbidities, first and foremost, to see if there are any particular medical conditions that might change how we think about subsequent therapies.

Then we also look at mobility, functional status, any history of falls, which, you know, I think are really key, especially when we think about some of our treatments that may require anticoagulation, et cetera. The third one would be cognition. So, I think that neurocognitive status is really important, especially now in our era of immunotherapies, which I think we'll get into a little bit later.

And I think about kind of baseline mental capacity and then how we're gonna observe patients, especially when we're thinking about bispecific therapies. And then I also look at nutrition and polypharmacy medications and see how we can manage that. So, those are kind of the main components that I look at when I meet an older patient, really going through and assessing those.

ASCO has some really great kind of basic guidelines that can be looked at. And then, once we've kind of identified perhaps any issues in those domains, we kind of are able to tackle how we take care of those and then really choose which treatments we can, you know, optimize.

[00:02:48] Joshua Richter, MD: And, and so much of what we talk about in myeloma is efficacy and toxicity data from clinical trials. But we recognize that trials tend to skew younger and fitter than the patients that we see day to day in clinic. So, you're sitting across from a frail 80-year-old patient. How do you translate the trial data that comes from all these, you know, international studies into the person who's sitting in front of you and really kind of personalize it for them?

[00:03:17] Larysa Sanchez, MD: I think that's a great point. You know, obviously, in the newly diagnosed setting now, we've had, we, we're seeing that daratumumab-based regimens work so well for older patients and tend to provide such long progression-free survivals now. But then the question becomes: how do we look at the kind of relapse data and understand how those outcomes that we're seeing in the clinical trial setting are going to translate to older patients?

So, I think about this kind of twofold, and I guess I'll talk about it more in terms of maybe, like, second-generation IMiDs, PIs, and also talk about it in the context of now our bispecific therapies, right? So, I think that our initial relapsed/refractory myeloma trials, especially the ones that were more dara-based, are now more difficult to translate because most of our older adults are getting daratumumab upfront.

And then the outcomes, unfortunately, in some of the, you know, second-generation PI, like carfilzomib, and pomalidomide-based regimens are not as optimal as we, we expect. And, you know, in a lot of these trials, dosages were perhaps higher than what we may give to, to older patients, so I think this is something to consider.

I think that if we're thinking about the context of those trials, we at least might dose-reduce agents such as carfilzomib, pomalidomide, in the, in the second-line setting. But I think the very exciting thing now is, you know, we, we have a lot of bispecifics available.

These trials also, I think, you know, do not include as much of the older adult population to be representative, although there is a lot of retrospective data that has looked to see how outcomes are in older adult patients compared to younger patients getting bispecifics.

And I think that, reasonably, we can think about a lot of our treatments, as long as we're dose-reducing and tailoring to older patients, as pretty safe and efficacious for, for our older adults.

[00:05:13] Joshua Richter, MD: I think you're describing this perfectly. You know, the devil is truly in the details, and we have all of these options, but can we adjust doses or supportive care to match the patient in front of us? And, interestingly enough, in the last episode, we really delved into patients who are ineligible or declining T-cell redirection.

But the concept of ineligible can really mean a lot of things. And in your world, who is actually not eligible for T-cell redirection therapy, and how much of that is fixed versus how much of that is something we can fix?

[00:05:46] Larysa Sanchez, MD: Yeah. So, you know, I mean, when we, when we think about older patients, there really is no defined age, right, to think about when we would not use CAR T, for instance. I think that we base a lot of this, again, on our clinical trials, where most of these patients for, for CAR T, for instance, are younger, probably younger than the age of 75, and there is really limited retrospective data on patients above 80.

So, when I think about T-cell redirection and if I'm coming to that juncture where I'm thinking about CAR T versus a bispecific for older patients, I think this is where the comorbidities are extremely important. So, I'm thinking about, you know, cardiopulmonary status and renal function, where maybe patients would not be able to tolerate lymphodepleting therapy for, for CAR T, right?

History of infections—potentially then you're thinking about your BCMA versus non-BCMA bispecifics. And then, basically, sensitivity to steroids for older patients may make it more difficult to manage things like CRS or ICANS, you know, in, in these types of contexts. So, generally, you know, I think that if I'm seeing an older patient above 80, I probably will lean more toward the bispecific in terms of T-cell redirection, especially when I'm just taking into account maybe multiple comorbidities.

But I think that in terms of bispecifics, I don't truly have an age limit because, again, they're really well tolerated, and we can reduce dosing frequencies to reduce infections in patients. And I've dosed patients as old as in their 90s with bispecific therapies.

[00:07:21] Joshua Richter, MD: So, that's something I really want to capitalize on. You, you have this amazing experience managing the day-to-day treatment of older patients with myeloma, and I really want to kind of, you know, pick your brain a moment. You know, for an older patient who's starting a new line of therapy, what surprises them the most, you know, as far as what treatment's actually like, and what are some of the gaps that you see between what the patients expect and what they actually go through?

[00:07:49] Larysa Sanchez, MD: So, I mean, I, I think that's a great question, you know, again, because I think our, I think our frontline regimens are so good, you know, especially patients who, for instance, maybe are on Dara-Rev maintenance now for, you know, quite some time after first-line therapy. If we're talking about early relapse, I think, you know, sometimes it's a little jarring for patients to have to think about, again, increasing frequency of, of coming to appointments, and I think that's especially true for, for older patients who may be having mobility issues, caregiver issues.

So, I think that's probably one of the biggest concerns for, for older patients: increased frequency of appointments. And I think that, you know, minimizing that is extremely important. So, you know, even thinking about bispecifics and being able to reduce frequency, I think that makes them, you know, really great options, I think, for our older patients because we tend to be able to go, you know, to monthly dosing if we're seeing really good responses, and that really decreases that burden overall.

[00:08:45] Joshua Richter, MD: I think we've hit on a few big, you know, therapies like CAR Ts and bispecifics, but let's drill down to therapy-specific considerations. So, we're gonna go through kind of the rapid fire. You know, I think many people listening are probably thinking about patients that have already gone beyond the core backbone of IMiDs, PIs, and monoclonals, and I really want to get your take on, you know, pearls of wisdom for our, our listeners to walk away from regarding older patients, frailer patients, with our modern-day arsenal—things like CAR T, bispecifics, belantamab mafodotin, selinexor, and, oh yes, the dreaded dexamethasone.

[00:09:24] Larysa Sanchez, MD: I'll start with the dreaded dexamethasone because that one might be the easiest one to think about. If we're incorporating that into the relapse regimens, you know, for all of my patients, certainly dose reductions, I think, are key for, for older patients to really minimize risk of edema.

You know, any cognitive issues, delirium, insomnia—all of that can happen with dex, so I would start at a maximum, I think, of 20 mg for patients, especially for, you know, adding it to a weekly regimen. But then, again, even for someone more, you know, frail, I would think about starting even lower.

So, certainly reducing that by at least 50%. Thinking about CAR T, I think that the biggest thing to think about, you know, are kind of probably the long-term side effects for these types of therapies. So, when thinking about our CAR T options, which are ever-expanding, I think, when we think about CAR T for older patients, really looking at the neurologic toxicities is really important for older patients and potentially picking, you know, a product that maybe has less of a risk for that, especially kind of like delayed parkinsonism that we can see.

And, you know, I think that there are a number of, of, of CAR Ts that offer that. So, that would be my preference for patients who are still eligible to go through CAR T and have the caregiver support. And then, overall, in terms of bispecific therapies, I think, you know, the, the number one thing to look out for is prior infections.

So, you know, as we age, you know, there is a change in the immune system overall, and I think that older patients are at a greater risk for infections. So, I think really optimizing bispecific therapies is important. So, especially for our BCMA bispecifics, really starting IVIG on a monthly basis for our older adults and staying on top of that, making sure that we're, you know, monitoring for any increased frequency of infections.

Because if we're starting to see that, we may want to minimize the frequency of dosing. And for a lot of my older patients, what I will do is I'll actually reduce the frequency pretty quickly. So, as soon as I see that VGPR response, I'm really trying to go to monthly dosing to decrease that risk of infection.

And then, you know, when we think about our other bispecifics like GPRC5D for older patients, I think it's really important to look at nutritional status. And this is something that can be, you know, looking at kind of weight prior to, to see if someone's at increased risk for these oral toxicities that we can sometimes see with these agents, because getting ahead, I think, is really important.

And, you know, aligning with the nutritionist, making sure to start supplemental agents like Ensure is really, I think, key for, for the GPRC5D agents. And then I think, what were the other ones that you mentioned? Belantamab. This is a drug that recently has come back to us, right?

And it is now an option for use. You know, I think we're still concerned about some of the ocular toxicities that we potentially see with this drug. So, I think, especially for older patients, quality of life, I think, is, is really key. And I think this is a toxicity important to explain because it may, again, require increased frequency of these visits, maybe going to an ophthalmologist.

So, I think that's an important discussion to have. And

[00:12:37] Joshua Richter, MD: And, selinexor.

[00:12:38] Larysa Sanchez, MD: Selinexor. Yeah. I, I found this agent to be great, especially as a bridge between certain amounts of therapies, and I think that starting at lower dosages—so, again, dose reduction, I think, is kind of key here for, for older patients.

So, starting at lower dosages, for instance, like 60 mg, I think, is, is key here, because that really reduces the risk of thrombocytopenia in, in older patients. Another important point about selinexor is considering also the potential GI toxicities such as nausea and vomiting that have been associated with this medication. So, what I tend to do, aside from just really reducing and using the minimal dose for selinexor, is I tend to dose weekly for 3 weeks on, 1 week off, to kind of help mitigate these toxicities such as thrombocytopenia.

And also really make sure to kind of stay on top of an antiemetic regimen for these patients, especially on the days of dosing. And considering low-dose Zyprexa, I think, is, is, is really key aside from, you know, Zofran and, and steroids as well.

[00:13:38] Joshua Richter, MD: Couldn't agree more. I think those are absolutely incredibly clinically valuable insights.

I really want to thank you so much for this valuable discussion. It's been an absolute pleasure to have you on today.

[00:13:51] Larysa Sanchez, MD: Thank you so much.

[00:13:52] Joshua Richter, MD: And with that, I'm Dr Joshua Richter. Thank you for joining us on Hematology Highlights.

This transcript was generated by AI and lightly edited for clarity.