In this interview in honor of Multiple Myeloma Awareness Month, Dr. Rahul Banerjee, a Clinical Fellow in Medicine at the University of California, San Francisco, and member of the Oncology Data Advisor Editorial Board, speaks with Dr. Neha Korde of Memorial Sloan Kettering Cancer Center about the potential of digital health tools to improve quality of life for patients with multiple myeloma.
Rahul Banerjee: Welcome to Oncology Data Advisor, a digital resource for the multidisciplinary cancer team. My name is Dr. Rahul Banerjee, and I'm one of the editorial members. March is Multiple Myeloma Awareness Month. I'll continue my interviews with various faculty across the country who are experts in important topics in myeloma that we sometimes don't talk about as much at our annual meetings.
Today it is my honor to speak with Dr. Neha Korde. Dr. Korde is an Assistant Professor in the Myeloma Service at Memorial Sloan Kettering Cancer Center. She has published extensively about two topics we'll be discussing today: one, quality of life among patients with myeloma, and two, the potential for digital tools, both passive and active, to help us care for our patients with myeloma. Dr. Korde, Neha, if I may, it's a pleasure to meet with you.
Neha Korde, MD: Thank you for having me.
Dr. Banerjee: Absolutely. I'll start with quality of life and why it matters to multiple myeloma patients. I know you and I are both familiar with that paper from a couple years back that actually showed that ambulatory patients with myeloma have worse quality of life than patients with any other cancer, including even pancreatic cancer. It's obviously not a competition of any sort, but it's telling for our patients. Why do you think that is? Why do you think quality of life is so historically poor for our patients that we treat?
Dr. Korde: That's a great question. I've actually thought about this a lot, more so since I've been digging into quality-of-life research and really trying to understand what it is that our patients are feeling and experiencing when I see them in the clinic. One of the things is that multiple myeloma is really sort of a unique disease where the disease symptoms and burden on patients are really extreme, especially upon disease presentation. Then the other thing is that we've made such great strides in terms of survival numbers and responses, and that's largely due to the fact that our therapies are so great. But in some respect, it's sort of a double-edged sword, because one of the things that we're telling our patients is, "You're living longer, but yet you're still not technically cured."
With all of that, there's a lot to unravel for our patients, because we're essentially telling them that they have this chronic cancer and disease burden that they're going to be dealing with for a long period of time. Not only that, but they have to still take therapy for all of these years; there's not a finite amount of time when they sort of stop therapy. They're generally on therapy for a long period of time. It's an emotional burden, and it's a financial burden because of the cost of these therapies. Then there are the toxicities associated with those chronic therapies. I think that's probably why we see such a huge impact on quality of life for our patients.
Dr. Banerjee: I completely, completely agree. As you said very well, it's not just the disease, but it's also the treatments. I agree that even our more sophisticated, newer molecular therapies, immune-based therapies, and small molecular inhibitors have done so much for our patients. They're living longer, but these new therapies come with unique side effects. In my mind, I believe that the more intensive the therapy, the worse the quality of life is, at least in the short term. For example, with stem cell transplant, I often think, "All right, if you choose transplant versus no transplant for a patient, the more intense the therapy, the worse they feel," at least in the short term. As you've pointed out in some of your prior works, it's not always the case. More therapy is not always worse quality of life. Can you give some examples of that?
Dr. Korde: Absolutely. Just like you said, we think that more drugs you add on—especially since we're going into this era of quadruplets and triplets—how is that really impacting the patient? One of the things is that number one, a patient's body is very individualized in the sense that it's such a complex system of organs and systems coming together. How are patients really experiencing some of those side effects? I think we can do a better job of really understanding what they're going through. When a patient has a high disease burden to begin with and you are throwing on therapy that is very efficacious, immediately you are going to get some sort of benefit for this patient.
One of the things is that it's a balance between what that particular therapeutic agent is offering in terms of efficacy and then reducing the disease symptom burden versus what side effects they bring to the table. Not to call out certain agents, but if you look at daratumumab (dara), for example, it's such a great therapy to add because of the bang for your buck of really decreasing the myeloma disease burden symptoms. It's not necessarily adding too much in terms of toxicity, especially from a subcutaneous administration point of view. It tends to work well for patients. We see examples of that in the Mayo Clinic data looking at quality of life, as well as the ASPIRE trial looking at carfilzomib. It's such a great agent in terms of efficacy, in that it sort of diminishes the disease burden symptoms right away.
One thing I wanted to bring up since we're on the topic of which agents are bringing what to the party when we consider these combination therapies—and in the field, we talk about this all the time—is that all of our backbone therapies have dexamethasone (dex) in them. I'd like to see our field kind of move away from dexamethasone, especially in our elderly patients. It really seems to impact the quality of life that patients are experiencing in their day-to-day symptom burden. If there's one thing I'd like to see us get away from, it's starting to address how we can get away from steroids.
Dr. Banerjee: I love that. Agreed. I think that the biggest study of steroid dosing in myeloma is probably over a decade old, where they did the high-dose dex: 40 mg for four days on and four days off, versus once a week. The lower-dose dex group had both improved survival and better symptom burden and fatigue, but 40 mg of dex every week is still a lot. Do you often go down to 20 mg weekly for your patients who are older or more frail? Or do you play it by ear and discuss the benefits and risks of it with them?
Dr. Korde: I tend to play it by ear and discuss the benefits. It really depends on the situation, but I'm very proactive about it in my older patients because I feel as if it's really affecting them and their ability to get through life day-to-day, especially their sleep.
Dr. Banerjee: Totally agree. Especially fatigue, in my mind, is one of those symptoms where I wouldn't think that once-a-week medication affects fatigue throughout the week, but when you talk to patients, they say, "Mondays are my worst day because that's my steroid days. Tuesdays are terrible. Tuesday through Friday is terrible. Sunday's great, and Monday's bad again." I agree that we can do better, and hopefully our generation will help move those trials along and make that a more commonplace thing for our patients.
Dr. Korde: The way you're explaining it is right. It's almost the up and down that is troublesome for some of our patients, rather than the steady, even flow. Steroids seem to have such a big impact on that, so I really hope we start to generate some data to get away from steroids.
Dr. Banerjee: Agreed. Conversely, I'll just echo what you said about daratumumab, which has really been a game changer here. I'm young enough but also old enough to remember when we didn't have daratumumab (dara) on our inpatient formularies. Our inpatients, who were obviously feeling crummy as they had the most symptom burden, were not able to get daratumumab as part of their induction, and now they are. I definitely think it's amazing that's it's an option for them, because you're right, that first cycle is where, if you move quickly, you can actively remove the symptoms, the pain, the fatigue, and the kidney issues that are causing the bulk of their symptoms. This actually might make them feel better not just within months, but within weeks.
Dr. Korde: Absolutely.
Dr. Banerjee: Maybe I'll pivot slightly into quality-of-life measurements and surrogates for quality of life. As you know better than anyone, there are a dozen possible instruments out there, and most of them are long. Survey fatigue is an issue. You've looked at wearable actigraphy—smart devices or smart watches or physical activity monitors—as a surrogate for quality of life and as an easier tool for patients to just wear and go on with their lives. Can you tell us a bit more about that research?
Dr. Korde: Absolutely. We're actually still in the process of compiling it and putting the final touches on the publication. What we did in this study was we took newly diagnosed myeloma patients who were treatment naive and put them into two different groups: a young cohort and an older cohort. We used age 65 as a cutoff. We took time to get some baseline data in terms of how they were moving, their activity, their steps, and their sleep. Then we also did those traditional patient-reported outcome surveys that we've been using in the myeloma field over decades. What we did was we then followed these patients with these wearable devices for six months, continuously, 24/7, and essentially got a bunch of different data coming back at us.
It's taken us a while to go through everything, but one of the things that's kind of striking is that when you look at the findings, it's pretty intuitive. You actually see from an objective standpoint that step count and activity are improving. When you compare baseline data with patients once they're on treatment, they do this recoverability where activity goes up. What's interesting is that you see more of a profound effect in the older patients. In the older cohort, their baseline activity steps were very diminished. One thing this tells me is that their reserve, their fragility, and their frailty index is lower. They're very much impacted by disease burden symptoms. As soon as you start treatment, you actually can objectively see that their step counts and their activity are increasing. It's kind of neat from that perspective.
The second point that we saw in our dataset is that when you look at activity, there seems to be some association with reduction of disease burden symptoms. There's an inverse relationship there. There also seems to be a direct relationship between physical functioning scores from the patient-reported outcome surveys, as well as an improvement in terms of global health scores. There is some relationship there in which patients are moving better and have increased activity. We actually see this relationship on some of these global health scores, so it's kind of intriguing to see that. We're in the middle of looking at the sleep data, as well. We see some really interesting intracyclic differences in sleep patterns when we're looking at patients on their dexamethasone days versus days when they're not getting their dexamethasone. You can actually pick up some of that, and it's an interesting dataset to analyze.
So it's great that we can use these tools, but where do we sort of see this all going? I'd be curious to see if we can take some of this data eventually and then create some sort of index score to really understand in real time how patients are feeling and moving and how that actually is translating into their quality of life. I'd like to be able to explore that a little bit more in terms of whether or not, for instance, increased activity can actually influence how patients are doing in terms of quality of life, so not just as a surrogate. Can we actually go the opposite direction where we're really, truly benefiting patients and benefiting their quality of life? I think that relationship is kind of interesting, and that gets into the difference between passive monitoring with these digital wearables versus active monitoring. Active monitoring implies that if we use a digital wearable or a digital therapeutic, we're actually influencing the patient's outcome in some kind of way. That's what I'm most excited to see and to explore this relationship.
Dr. Banerjee: Agreed. I'll just add that we make decisions based on how we presume a patient's physical activity is all the time: transplant eligibility versus ineligibility, Eastern Cooperative Oncology Group (ECOG) performance status, and so forth. Do you see a role where this might actually help in some of those treatment determinations from the provider side?
Dr. Korde: That's kind of where I'm wondering if it could potentially go down the line. If you're getting little bits of data every minute to an hour, how does that compile into decision making? Should it influence whether we go up on the dex or go down on the dex? Do we go up on this dose, or do we go down on this dose? As you go through it, the possibilities are sort of endless, as long as we have a tracker to track or monitor a particular symptom or side effect—for instance, if we had a tool that could really help us measure neuropathy in real time and what that's doing to a patient. I'm not saying such a tool exists yet, but if it did, that would be kind of interesting. We could use that to influence our decision-making capability in the clinic, and I think it would actually end up helping patients because it's almost tailor-made to what's going on in their situation.
Dr. Banerjee: Completely agreed. The last question I'll ask is pivoting to how you mentioned passive versus active monitoring and tools that can actually be used as digital therapeutics. In my mind, that can range from a device that tells you how you're walking, to a smart pill bottle that helps you remember to take your lenalidomide, to digital coaching or cognitive behavioral therapy delivered through an app. Are there particular digital therapeutics that you're working on or that you're excited about, or both, in the coming decade?
Dr. Korde: Absolutely. Two situations pop into my mind. One of them is more in the maintenance phase when patients are doing a reset: post-transplant, when they're on their maintenance and they're kind of getting readjusted to this new way of life. They've gone through this whole tremendous year of experiencing the onslaught of getting a diagnosis, going through induction, then going through transplant. As you are well aware with your digital coaching experiences and research, it's so traumatic to the patient. By the time you come around to explaining to them about maintenance therapy, it's almost as if you have to walk them through a mind reset.
I think that there's a lot that we can do there in terms of really addressing quality of life. For instance, there could be a digital health application tool where patients are really honing in and connecting with their patient peers, possibly getting diet and nutrition and exercise tips, in a real connection hub that's online and on-the-go. I really wonder how something like that can actually improve health care outcomes for our patients and get them to this new reset. The second thing, which is completely fascinating, is that as we move into this era of chimeric antigen receptor (CAR) T cells versus bispecifics, we're so adept at giving these therapies in the hospital as inpatient. It would be interesting to see how some of this can be done as an outpatient and what digital tools can be used in terms of outpatient monitoring therapy. For instance, is there a digital signature that suggests an early cytokine release syndrome (CRS) onset or a CRS severity index that would imply that we should have a therapeutic intervention early on? I think that this would be fascinating if we could use digital wearables to actually treat patients or make some informed clinical decision.
Dr. Banerjee: I love that, and I totally agree. When people give the kind of argument of, "Well, who's going to pay for this new wearable tool?" I would argue that saving the patient one night in the hospital probably pays for itself in terms of the cost of this digital technology for them. This has been very, very informative. I love your analogy about resetting how patients live their life. I use the analogy of helping patients regain control of their lives as they move into the maintenance setting, but the same principle applies. There's such a profound difference for them in both the relapsed CAR T and bispecific space as they're moving into maintenance. I think there are a lot of unmet needs and a lot of potential for digital health there.
Thank you again, Dr. Korde, for your time. This was very eye-opening for all of us. To everyone in the audience, thank you for listening. I am Dr. Banerjee, and this has been Oncology Data Advisor. Thank you again.
About Dr. Korde and Dr. Banerjee
Neha Korde, MD, is an Assistant Professor in the Myeloma Service at Memorial Sloan Kettering Cancer Center in New York. She specializes in the treatment of patients with multiple myeloma and other plasma cell neoplasms. Dr. Korde's research focuses on understanding the disease biology surrounding the transition from MGUS and smoldering myeloma to active disease, as well as utilizing digital health to improve quality of life for patients with multiple myeloma.
Rahul Banerjee, MD, is an advanced clinical fellow in Bone Marrow Transplant/CAR T-cell therapy at the University of California, San Francisco (UCSF). Most recently, he has joined the multiple myeloma faculty at the University of Washington Fred Hutchinson Cancer Center in Seattle. His clinical interests are in multiple myeloma and AL amyloidosis, and his research interests are in CAR T therapy, digital health, and care delivery.
For More Information
Stewart AK, Dimopoulos MA, Masszi T, et al (2016). Health-related quality-of-life results from the open-label, randomized, phase III ASPIRE trial evaluating carfilzomib, lenalidomide, and dexamethasone versus lenalidomide and dexamethasone in patients with relapsed multiple myeloma. J Clin Oncol, 34(32):3921-3930. DOI:10.1200/JCO.2016.66.9648
Rajkumar SV, Jacobus S, Callander NS, et al (2010). Lenalidomide plus high-dose dexamethasone versus lenalidomide plus low-dose dexamethasone as initial therapy for newly diagnosed multiple myeloma: an open-label randomised controlled trial. Lancet Oncol, 11(1):29-37. DOI:10.1016/S1470-2045(09)70284-0
Kent EE, Ambs A, Mitchell SA, et al (2016). Health-related quality of life in older adult survivors of selected cancers: data from the SEER-MHOS linked data resource. Cancer, 121(5):758-765. DOI:10.1002/cncr.29119
Tavitian E, Mastey D, Salcedo M, et al (2018). Continuous mobile wearable bio-monitoring of newly diagnosed multiple myeloma patients undergoing initial chemotherapy [poster presentation]. Blood (ASH Annual Meeting Abstracts), 132(suppl_2). Abstract 4751. DOI:10.1182/blood-2018-99-116545
Hevroni G, Mastey D, Tavitian E, et al (2021). Using mobile wearables to establish sleep bioprofiles in newly diagnosed multiple myeloma (MM) patients). J Clin Oncol (ASCO Annual Meeting Abstracts), 39 (suppl_15). Abstract 8040. DOI:10.1200/JCO.2021.39.15_suppl.8040
Transcript edited for clarity. Any views expressed above are the speaker's own and do not necessarily reflect those of Oncology Data Advisor.