Watch Dr Hira Mian (McMaster University, Hamilton, Ontario, Canada) review the 10th World Congress on Controversies in Multiple Myeloma 2024, focusing on:
Managing older and/or frail adults with multiple myeloma (MM)
Guidance on using frailty scores for managing relapsed/refractory (RR) MM
Treatment advances in the RRMM space
It's really great at COMy to actually have separate sessions dedicated about real-world outcomes. And Philippe Moreau, I believe on the Friday present, had a great presentation about some of the real-world data that was presented at COMy from some of the newer T-cell redirecting therapies. So I think one of the important parts is that when we're seeing a lot of this real-world data, sometimes we're seeing data that still has a short follow up period, and he highlighted that it's important to put those results in context, that we really do need to understand, even in the real-world outcomes, a little bit over longer term to really make sense of that data. So I'm really glad that he highlighted that part. Both in my presentation as well as in lots of the other presentations we highlighted that there were potentially some increased toxicities with some of these T-cell redirecting therapies seen among older adults as compared to younger adults.
So to give you one example, you know, there was a large study that was published by CIBMTR with one of the myeloma CAR-T products, which showed that perhaps rates of CRS and ICANS were slightly higher in those of older adults. So I think, again, once we moved these therapies out into the real-world, we'll need to continually evaluate that data to see how it translates over, and particularly how it translates over to patients who are often underrepresented in clinical trials. But I think I really like Dr. Moreau's caveat as well that we do need to sit tight, be patient as well, and ensure that our real-world data does have longer follow up so we can accurately understand it.
"It is important to put real-world data in context... we need to view them in relation to long-term follow-up." Dr Mian. View transcript .
So I think, you know, in the past few years we're learning more and more that a patient's chronological age is not necessarily equivalent to their functional age, and that frailty scores are one particular modality to really understand what a patient's functional status is, and why that's important in myeloma because it allows us to understand what their tolerability for treatment is, and what is their toxicity risk like. So I think, you know, at this time, a lot of the frailty data that we have uses some of the scores that have been well established, but that are mostly in the newly-diagnosed setting.
Both in my talk and there was another frailty talk as well at COMy, we both highlighted that some of these tools really do need to be validated more in the relapse refractory setting, and probably we do need to look at what parts or components of these tools, or do we actually need novel tools that will help us better predict some of the unique toxicities that older adults will have with modalities like bispecific antibodies or CAR-T, so do we really need newer frailty assessments as well that perhaps include some cognitive testing as well? So I do think, you know, we're really just scratching the surface of some of these frailty assessments.
Dr Mian outlines the potential gains of using frailty scores in RRMM and considers whether the existing scores are fit for purpose. View transcript .
So again, in relapse refractory multiple myeloma, I think, you know, we're seeing, again, lots of activity with T-cell redirecting therapies. We're seeing a lot of these therapies that we're used to seeing some of the data in greater than three or four lines of treatment. We're seeing that data being moved in earlier lines of treatment. So we already, across the world, in many parts of the world, cilta-cel, for example, is being moved to an earlier line of treatment and there's additional clinical trials that will in fact be evaluating in first line of treatment.
So I think in this relapse refractory setting, we're seeing a shift in a lot of those therapies that have been very exciting in moving it earlier. You know, it remains to be seen how the efficacy and durability is as well as some of the toxicity. So even at this COMy, there was a lot of discussion around what toxicity is tolerable or should be accepted, especially as you move some of these therapies up front. So I would say in the next few years, you know, we'll see a lot of activity probably in that one to three prior lines or potentially even be in the newly diagnosed setting as all of these therapies get moved upfront.
"We are seeing lots of activity for T-cell redirecting therapies being moved to earlier treatment lines." Dr Mian. View transcript .
So, I think for this one, you know, it's similar to when we think of treating a younger patient. You want to think of patient-specific characteristics, disease-specific characteristics, treatment-specific characteristics. So, an older adult, that patient-specific characteristic includes a frailty assessment. It includes also their social setting. Do they live alone? Do they have a caregiver? And also, increasingly, we're becoming aware of what would the patient want and what would their preferences be, especially in that relapse/refractory setting. I showed at COMy that there was data published earlier this year that, in fact, showed that 75% of older adults would actually pick better quality of life and functional status and cognitive status over outcomes like overall survival. So I think when we think of that bucket of patient characteristics, we really need to think about that particular aspect as well.
On the second hand, we do need to think of disease characteristics. You know, so it's similar. Does this patient have high risk cytogenetics? Are they progressing with a biochemical or a clinical relapse? What's the tempo of their progression? Because that ultimately decides what types of options and what the timing of those options will be. And on the third hand, we need to think of treatment-related characteristics. So we talked about proteasome inhibitors, for example. Does my patient have underlying neuropathy from previous exposure to proteasome inhibitor or previous toxicities that are still ongoing and will that limit my ability to what newer drugs to give to them? So I think both patient disease and treatment-related characteristics all together should inform how we treat older adults with relapse/refractory myeloma.
View transcript .
View transcript .
So I would say one of the key highlights is that COMy is going to become an increasingly important and probably one of the pivotal meetings in myeloma. So every year when I go, I'm kind of surprised to see just how big and how important it is getting. I think that we're seeing lots of great data, but what I really like about the COMy meeting, and I like the way that it's framed around the controversy. So I think in myeloma now we're in this fantastic position where we can actually talk about options. And so one of the best parts for me about COMy is talking about some of those controversies, you know, so we had some great debates from folks about how to treat smouldering myeloma or what the best options are for smouldering myeloma. And similarly, even for my session around the relapsed refractory myeloma, what some of the options are.
So I think for me, the key highlights from COMy's are the discussions with colleagues along the issues that are actually controversial and hearing other people's perspectives. I think the other part that is actually quite unique about COMy is because it is truly a really international audience, you know, with a huge presence online as well, is that you are getting those very different perspectives. So, you know, when I give an option and say, "I would treat this patient with a T-cell redirecting therapy," I'm quickly reminded by members of the audience that I work in a very resourceful area, and that for most of the world, that therapy may not be accessible. So I think COMy also brings some of the inequities and really highlights how we really need to do better as a global community as well when we start to have some of these discussions around therapy.
Dr Hira Mian