Ryan Haumschild, PharmD, MS, MBA: One of the things we’ve talked a lot about is [that] multiple myeloma might be a disease of aging and there might be some frail patients. As you mentioned, there could be a doublet that might be too intense for some patients. It's always interesting when we can look at some data analysis around frail patients. Dr Lipe, I’m going to look to you a little bit. In the MAIA trial [NCT02252172], there was some analysis and we can use some of that information around frail patients. How do you look, in your practice, at defining who is a frail patient, and then how do you treat frail patients in your real-world practice?

Brea C. Lipe, MD: I think that that is an emerging field in myeloma. As we know, this is a disease of the aging, so we really need to make sure that our treatments are adapted to the population that we see, so our trials have to reflect these patients. We have to understand the toxicities and how to modify them. I think that, in practice, it’s actually been humbling for me because I know these people; these are my patients. They come in, they meet me, and I hear their stories. But then when you actually do real assessments of these people to understand their frailty status, the assessments ask questions that they might not be so forthright [about] in a casual conversation, such as “Are you able to do your activities of daily living without assistance? Can you put your own socks on? Do you cook your own meals?” And those are not necessarily things that they come into clinic saying, I don’t do these things. I think it’s really important to recognize in our trials and to design trials for the patients that we actually see. In the subanalysis it was a retrospective analysis, but they characterized patients as fit vs intermediate-fit based on the trials and comorbidity index and the ECOG [Eastern Cooperative Oncology Group] scoring system. Patients were divided that way, and what they found is that, as one might assume, frail patients didn’t do as well as patients who are intermediate-fit or fit. But when you actually looked at those subpopulations and compared how they did amongst the 2 arms––DRd vs Rd [daratumumab, lenalidomide, and dexamethasone vs bortezomib, lenalidomide, and low-dose dexamethasone]––they found that even in the most frail patients, those patients who [received] DRd did better than the patients who didn’t [receive] the daratumumab. This tells us that our therapies have come to the point where the toxicities are manageable enough that we can actually treat our patients with real effective therapies and not compromise their quality of life. The other thing that we saw in the MAIA trial [data] is that quality-of-life scores improved across the board, and I think that’s a powerful thing. In clinic, when I’m assessing people and trying to establish where they are, I think that we need to move away from the dichotomy of transplant eligible vs ineligible, because that’s historically based on when we gave melphalan and we couldn’t collect [data], and we don’t really use melphalan a lot [now] in this country in many settings. I think it’s important that we reevaluate patients over time, because so many of the comorbidities that they face are related to the myeloma, and their mortality. I think we really have to reevaluate patients over time. Geriatric assessment is the gold standard for how we do that; it’s not available everywhere, but there are good calculators that you can get. I’m personally a fan of…the IMWG [International Myeloma Working Group] frailty calculator because that incorporates both comorbidities, like the trials index, but it also incorporates those activities of daily living. There have been studies looking at how effectively and efficiently those can be done in the clinic setting, and it’s not as cumbersome as it might seem. I was one of those people that thought it would be way too cumbersome, and it turned out it wasn't. The data that I got from that were actually quite helpful, because sometimes it was the patients who came up frail [about whom I’d say], “What do you mean? They’re great; they’re so wonderful.” There was a lot more that I didn’t necessarily appreciate because in our casual conversations, I wasn’t really appreciating what their life was like at home.

Raymond Thertulien, MD, PhD: I totally agree, and to extend that thought, there were a lot more subanalyses done in the MAIA trial. One thing that we deal with often in the myeloma world is patients with renal failure, for example. I was very surprised to see in those subanalyses that patients who had some renal insufficiency with creatinine [levels] less than 60 [µmol/L] still did as well as patients with normal kidney function, so the regimen itself is very adaptable to the population that we see in multiple myeloma, as Dr Lipe mentioned.

Ryan Haumschild, PharmD, MS, MBA: Those are all great points about being able to stratify patients, and they’re all bringing unique things to the table. They all have treatment history or different renal functions. If you have a therapy that can be adaptable so they can still perform well, I think that’s a good thing. And I think the toxicities can’t be understated. If a patient’s going through toxicity, it plays a huge role in their motivation to stay on treatment and stay adherent to therapies outside of the setting when they’re in clinic. If their quality of life can be maintained, they’ll have that motivation for treatment and they’ll stay adherent. That’s really where we see those outcomes that we’ve seen so well in the clinical trial translate to real-world practice. Thank you all so much for those different thoughts around the subgroup analyses and the learnings we can take away from that.

Transcript edited for clarity.