Oncology Data Advisor: Welcome to Oncology Data Advisor. Today I'm here with Dr. Kelly Brassil of the University of Texas MD Anderson Cancer Center and Dr. Rahul Banerjee from the University of California, San Francisco.

Rahul Banerjee, MD: Thank you for having us. As we'll talk about, this is a really exciting area of research interplay between digital health supportive care and bone marrow transplantation, but it's not the traditional route of research that a lot of institutions engage upon. It has really taken a village to get this study off the ground.

Oncology Data Advisor: So what are some of the most significant quality-of-life impairments that can affect patients undergoing ASCT for multiple myeloma?

Dr. Banerjee: This is autologous stem cell transplantation, or ASCT, where the heavy lifting is done by chemotherapy. Basically, it is a very, very high dose of chemotherapy against myeloma that knocks out the normal bone marrow. We actually pre-collect the patients' own bone marrow cells from the blood and we put them back into the patient after the chemotherapy has been given to rescue their bone marrow from the toxicities that they would have otherwise. The reason I say that is that this dose of chemotherapy is not really used in any other type of disease or malignancy apart from certain types of lymphoma or testicular cancers. It's just very, very intense.

We'll talk about how patients with myeloma have a lot of quality-of-life issues, but most of them are generally ambulatory. Most of them are walking around trying to stay fit; they're responding well to the chemotherapy that they've already gotten, which is lower-dose and often given in clinic. Then all of a sudden we tell them, "Now we're going to give you a giant dose of chemotherapy that will make you be in the hospital for two weeks or will make you have to come in and out of clinic every day for two weeks. You'll be miserable for a month, sometimes even two months; it'll take about two to three months to get back on your feet again." It's a very lengthy and involved process. We know that it works in myeloma; It doesn't cure myeloma, but it helps to kick the can down the road for longer. It's been shown to prolong progression-free survival, but it's a lot.

Clinically, as physicians, nurses, pharmacists, and members of our health care team, we're really good at managing symptoms and managing the myeloma. I think we're not nearly as good at managing quality of life or wellness, because we're just not trained in that domain. There's no medical school class or nursing class. That's where digital life coaching and health advisors come in. I think it provides a really unique element to support, as we'll talk about. Why particularly during transplant? Some of the particular quality-of-life studies have shown that quality of life nosedives after transplant; it takes about two weeks to hit its minimum and then slowly comes up thereafter. Anxiety and depression go up after transplant. Fatigue definitely goes up after transplant. Again, two weeks or so after transplant is when people are feeling the worst.

Other broader quality-of-life impairments—our group at UCSF has found that a lot of our patients are started on benzodiazepines in the week or two after transplantation. Benzodiazepines are used for anxiety or sleep but have lots of long-term side effects and are linked with fractures, falls, and delirium in older adults, like many of our myeloma patients. They're also difficult to deprescribe. Once you start a benzodiazepine, people stay it long-term. That's an example of how even this short-term quality-of-life deficit from transplantation can have long-term side effects.

Other studies have shown that higher anxiety after ASCT is linked with higher rates of posttraumatic stress disorder (PTSD) afterwards. Studies have shown that long-term quality-of-life impairments can occur in some patients who have a lot of anxiety during or after transplantation One recent European study found that only about a third of patients with myeloma who were working going into transplant were able to return to work after transplantation. Obviously, that's a big driver of quality of life for these people who are very functional going into transplantation. There's a lot to unpack there, and it's not something that 10 minutes a day when the doctors are rounding by a room in the hospital or a 15-minute clinic visit afterwards can really move the needle on. That's why our patients deserve and warrant another layer of support, and that's where this life coaching comes in. Anything you want to add there, Kelly?

Kelly Brassil, PhD, RN, FAAN: Absolutely. To build on that, we know that for the multiple myeloma population before they get to transplant, typically they've had another course of treatment. They tend to have both disease-specific frailties as well as treatment-related sequelae, and that can be compounded by multiple courses of treatment, as you heard Dr. Banerjee reference. There are patients with multiple myeloma who sometimes have more than one ASCT. It's a compounded effect that certainly influences quality of life. That's very important to consider when treating these individuals.

Dr. Banerjee: As doctors, we're so used to seeing patient undergo transplantation that we assume, "All right, just give it two or three months and everything will be back to normal again." I don't know that this is necessarily the case. That's where the health advisors can help patients rebuild their lives after transplant, knowing that the life they rebuild may not be the same as the life that they had before what happened.

Oncology Data Advisor: In your recent pilot study, how did digital life coaching improve quality of life for patients with multiple myeloma undergoing ASCT?

Dr. Banerjee: The short answer is that we don't know for sure whether our single-arm pilot study improved quality of life. This pilot study, which is completed, was geared at seeing whether this technology was feasible during transplantation. The phase 2 studies that are ongoing will help us really determine whether in a randomized manner, quality of life improves with life coaching versus usual care. The pilot study was geared for two reasons. One: just to test out the interface. I think there are a lot of differences in the transplantation period, including that patients are hospitalized for two weeks and they're really going from feeling very well to very crummy and back to very well again. Every week, things are changing versus a more static ambulatory population where they're just living with their cancer. That hadn't really been investigated. We wanted to see whether patients will even engage with their coaches in a meaningful way during transplantation. While they're hospitalized, people really are feeling crummy. They are constantly being moved around for tests. They're getting X-rays and getting labs drawn and might be away from their phone if they have it. They're not getting very good rest at all. Hospitals, as you know, are not known to be havens of sleep for our patients. They may not be willing to even speak with someone.

Then course, the health advisors. The life coaches that are called health advisor at Pack Health are not people that they have personally met before. The question is, going into this big procedure, are patients even going to want to speak with someone who may be able to help them in the long term, but who they haven't met before, particularly our patients who are older? Prior studies suggest that maybe older people don't use cell phones as much or as well. Essentially, we did show that this platform was feasible. Patients were very interested in this. We screened 18 patients for this pilot study; 15 of them ended up enrolling. Again, the three who didn't said that they had existing resources or wanted to speak with someone whom they knew and not someone whom they don't know; but 15 out of 18 is 83% of the patients interested in the study—even though it entailed using their phone more, even though it entailed talking to a stranger, and so forth. Of those 15, two patients didn't end up initiating the program. For one, the timing didn't work out to connect with the coach and one ended up declining before they started. We had 13 patients who we actually tracked.

To be honest, we were hoping to see that the patients would meaningfully speak with their physician at least once a month. I know that sounds like a very low bar, but that's the bar that other studies have set in the transplantation period because patients are busy, they're not feeling well, and so forth. To our happy surprise, we saw that bidirectional conversations—meaning patients actually speaking with their coach by phone or by text, back and forth—happened once every 7.6 days on average. About once a week, patients were meaningfully speaking with their coach, and then similarly even while they were hospitalized. Looking at just that first 28-day period where patients are feeling the worst, conversations happen once every 6.5 days on average. When patients were hospitalized or recovering from transplantation afterwards, they felt that they could connect with their coach and actually did about once a week on average.

In terms of our patient-reported outcome (PRO) data, there's no control arm here, so take these with a grain of salt. We did see that quality of life came down and came back up again, as predicted. Again, around Week 2 after transplantation, where patients feel the worst, that's generally the time when their bone marrow is starting to recover from transplantation. That wasn't that surprising. One thing that I found a little bit surprising is that prior studies really say that everything is worse in that second-week period, what we call count nadir after transplantation. We found that anxiety and sleep were about the same throughout the period, at least in our cohort. Sleep disturbances didn't get that much worse while patients were hospitalized. What I found the most interesting—and it was a good lesson learned for me—is that emotional distress about transplant, myeloma, and so forth would also be worse at count nadir when patients are feeling the worst, about to leave the hospital, or going back home after the transplantation. We actually found that in our pilot study that distress was highest before transplantation. In retrospect, that totally makes sense. I think patients were most stressed out about the uncertainty of the transplant itself, more so than of the recovery thereafter, but I think it was a good lesson learned for us because we actually started a pilot study in the first week before transplantation.

Patients would be paired with a coach five days before they got the cells back for the transplant. That correlates to three days before they came into the hospital for their chemotherapy. We realize that well, if patients are most stressed before the transplantation and not during or immediately thereafter, then maybe meeting with the coach only a handful of days before they're hospitalized is not sufficient for them to really get to know their coach and vice versa. We moved back to start it for our ongoing phase 2 study to Day -10, so 10 days before the cells go back in for their transplantation. That will hopefully make patients able to connect with their coach in a meaningful way and just have that intake call to understand, "What are you worried about? What are your strengths? What do you want to work on?" and so forth.

Dr. Brassil: Absolutely. I think as Dr. Banerjee mentioned, this was not powered to detect statistically significant difference between these groups. The data here is purely descriptive from the pilot, but the trends are consistent with our larger overall dataset for individuals with a cancer diagnosis participating in the digital health coaching—particularly around mental health and distress, anxiety, and depression, where we do see a measurable, and at times, a statistically significant change in these outcomes with improvement over the course of the coaching period. We're hopeful that our now-randomized control trial, which was presented at ASH as a trial in progress, will demonstrate some of these trends that were observed during the pilot phase.

Dr. Banerjee: The randomization is important because there's some selection bias as to which patients, for example, speak English, which is an eligibility criterion for this current iteration of the study. Hopefully it's something that we can take care of and fix later for our non–English-speaking patients, but within the parameters of selection bias, we want to randomize to really get a sense that it's the coaching itself that's actually making a difference for these patients. Something that I've learned during this time period in terms of best practices for interventional research is that there's certainly some element of what we might call a placebo effect or what you might more accurately, in this setting, call an attention effect. If you just keep telling patients, "Hey, we really care about your wellness and we've paired you with a coach," patients are going to feel better just because they're thinking about it. They're actively taking steps to work on their wellness and so forth just by virtue of being told to focus on it.

We are engineering our phase 2 study a little bit in that the intervention arm is receiving the full three-month package with the coaching, from working with their health advisor over the course of three months beginning at Day -10 before transplantation. Both arms, really, are receiving some generic handouts that we've put together that are just about wellness every one to two weeks. Again, the reason for that is because it's allowing both arms to benefit at least a little bit from the study in terms of getting some resources they might not think about otherwise. It's allowing us, not in a purely foolproof way, but at least somewhat, to allow both arms to really be thinking about their wellness and account for that element of increased attention to wellness, and then hopefully isolate what is actually being added from the coaching on top of just these handouts alone. Anything you'd like to add, Kelly?

Dr. Brassil: Absolutely. I think that as you heard Dr. Banerjee reference earlier, the majority of care for these patients is actually occurring outside of the clinical setting posttransplantation period. Some institutions are even infusing autologous stem cells in the ambulatory setting. The ability to support an individual sense of awareness and control over their condition post-transplant is really vital to their outcomes. We want to make sure that people feel empowered, that they know what to expect, and that the education that's provided in that hectic pretransplant period—even in the context of a hospital setting—is reinforced, so that individuals are both prepared to report symptoms and side effects early and often if and when they occur, and that they also have the ability to plan for what they might do should side effects or setbacks occur, or should they not be recovering in a physical way as quickly as they once anticipated. By empowering people with a plan around this, we know that even if coaching and other interventions can't completely eradicate or prevent side effects and sequelae from occurring, we can empower patients to be proactive in their own health and feel like they have control over that process with a plan. That's where the coaching is really pivotal to the outcomes of this work.

Dr. Banerjee: Completely agree. I think one of the challenges that certainly we face when we discussed these manuscripts and these abstracts was, well, why not have the coaches just be employed by UCSF? Why not just have them be at the institution itself? I actually think that there's a nice firewall between having the coaches be from a qualified, very, very highly functional coaching company like Pack Health, just because there are certainly some wellness and clinical matters that really come together. I think the coaches have done a really good job in situations when the patient comes to them saying, "Look, I'm having really bad neuropathy," or, "I have a fever," for example. A fever is very much our jurisdiction: the physicians and nurses should know about it at the treating center. They refer them back to us to remind us of that and tell us about that symptom and so forth. But I want them to feel like they have someone they could speak to about broader determinants of quality of life in terms of, "I'm not sleeping as well as normal. I just feel frustrated. I'm not getting back to being physically active as quickly as I would like," and so forth. They're obviously always more than welcome to bring those things up to us, but I think a lot of times, if they do, we don't have much to offer them except just to say, "Look, this will pass, time will pass, things will get better." The health advisors at Pack Health have a more structured and more patient-friendly toolbox to deal with that, because they're actually trained to deal with this and we are not.

Oncology Data Advisor: So what is the role of PRO in this study?

Dr. Banerjee: In the phase 2 study, our primary end point is benzodiazepine usage. As I mentioned to you earlier, a lot of our patients historically were prescribed benzodiazepines or Z-class medications. Again, it's hard because patients need to sleep. They're feeling quite anxious and these medications do work for those conditions—no doubt about that—but they have a lot of long-term side effects, particularly in older adults, which many of our patients with myeloma are. The median age at diagnosis for patient with myeloma is 69, so these are older adults by and large. We transplant patients routinely into their late 70s, sometimes even early 80s. A lot of our patients are in the boat where the risks of benzodiazepines outweigh the benefits in terms of delirium, long-term dependence, fractures, motor vehicle crashes, all sorts of things linked to these medications. Our study initially was designed to look at that as a primary end point between groups. Since our initial data came out showing that a lot of our patients get prescribed benzodiazepines and those who are prescribed them stay on them long-term, even presumably after their anxieties and they get better, our department took a soup-to-nuts approach to fix that problem. Our nurses were actually the champions of trying to reduce the prescription of benzodiazepines across the board during transplant and then for all of our hospitalized patients.

My suspicion is that we probably won't see a difference between arms on that because our center has appropriately responded much more nimbly than I was expecting to fix that problem, which is good. I think PROs will end up being the biggest thing that we look at between the two arms. As Kelly alluded to, even if we can't prevent quality of life from going down after transplantation, the area over the curve in terms of longitudinal modeling and how deep the quality of life falls from baseline, I do expect that to be better between one arm over the other. I would love to see whether the resolution of some of the quality-of-life impairments happens faster in the digital life coaching arm, because they are longitudinally empowered with tools to really understand what's preventing them from getting back to that quality of life and working with them to get there. Everyone will get better eventually by and large, but I think maybe it can happen faster with the addition of coaching.

Dr. Brassil: It's very important to us that we're including PRO measures that are well reported and well adopted in the oncology community. For this study, we're leaning heavily on PROMISE measures, which continue to be a primary tool used both in clinical trials and then also increasingly in the clinical care setting. In addition, we use the National Comprehensive Cancer Center (NCCN) Distress Thermometer, which is well adopted. Our goal with PRO usage is essentially threefold. The first is that the PROs actually inform the coaching experience for the members. As patients are completing these PROs, health advisors are utilizing that data to help address areas where they may have seen a dip between measure points and to be able to then support individuals with evidence-based content to address a particular concern, as well as to escalate up for clinical intervention as needed with the UCSF team. That partnership is critical to collecting data not just for data's sake, but really for the purpose of serving the patient first. Beyond that, we also can use this data to track and trend. There's a natural nadir that happens with cell count, but it also happens with PRO, where we do see well-documented in the literature an expected decline particularly in health-related quality-of-life outcomes during the most intensive posttransplant period. What we're hoping in this phase 2 randomized control trial is to be able to detect if the recovery from that nadir in PRO happens naturally as a result of the recovery of the patient or if there is a synergistic effect with the coaching that helps to accelerate and improve the benefit of that recovery. Finally, we can use this data to track and trend across pre-existing data for the multiple myeloma population. Certainly there's an increasing and ongoing need for attention to PROs.

As we use tools that have been utilized either in the context of clinical trials or the real-world setting, we're able to compare our dataset with the trends we are seeing more broadly across this population. How can we use that information to really inform our ability to potentially detect outcomes sooner or anticipate when a decline may occur? There was a study that was just reported that looked at the use of PRO and its correlation to being able to predict decline in other physiologic or clinical end points. This is very important to us as we try to better support the multiple myeloma population, particularly as new and emerging therapies occur for these individuals. We're really excited to be able to contribute to that science through our work in this protocol.

Oncology Data Advisor: What role do you foresee digital life coaching will play in this patient population in the coming years, and how do you recommend that it can be implemented into practice?

Dr. Banerjee: Two things I'll say. One, the existing product needs to be as scalable and implementable as possible. I think a lot of interventional studies have tried things ranging from acupuncture to music therapy to massage therapy during transplant to help to improve wellness. It's just hard because they're limited by the availability of those practitioners and because it's very difficult to move those resources between sites in a standardized manner. The advantage of this is that the cohort of coaches employed at Pack Health can really work with multiple sites that are very standardizable between institutions, which is important to make this more widely adoptable.

We still have some challenges. I think we're still working on figuring out how to address patients or caregivers who don't speak English. But I think the caregiver piece we haven't spoken about is also quite important, because the caregivers for these patients are also skipping work and undergoing a lot of stress. For patients or caregivers who don't own phones themselves, do we give them an iPad? Do we use landlines? Things like that are the future directions that we're going to work on. I also think the possibility of wearables devices to track physical activity would be a really nice complement to this. The data on wearables for physical activity in myeloma is a bit more mixed, because it seems like a gimmick to some patients. If you give a patient a Fitbit, that's often not enough to motivate them to use it and improve their wellness and physical activity. If you pair that with a life coach who's able to see the data and work with them, you might get a really good synergistic effect. Kelly is the expert here, so I'll let her take it from here.

Dr. Brassil: I think everything that you've spoken to, Dr. Banerjee, is so spot on. In fact, we are collaborating with new studies that will be launching in early 2022 that are going to examine just these outcomes on the impact of wearable technology. There's exciting work that's also been funded by the FDA focusing on how we might be able to correlate patient-reported wearable and clinical data again in some type of predictive capacity. That's going to be a really important future direction. In terms of our work, we're expanding these studies to move beyond the transplant space into further down the trajectory in multiple myeloma for the relapsed/refractory populations. We are really looking forward to seeing how we can apply this model across the multiple myeloma continuum to continue to support individuals to live their happiest, healthiest lives as they move forward from these various types of therapies, and also certainly for this population as they manage multiple myeloma as a chronic condition.

Oncology Data Advisor: Well, thank you so much for joining us today and sharing this great research with us.

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About Dr. Banerjee and Dr. Brassil

Rahul Banerjee, MD, is a Clinical Fellow in the School of Medicine at the University of California, San Francisco. He specializes in bone marrow transplantation and chimeric antigen receptor (CAR) T-cell therapy for patients with multiple myeloma. Dr. Banerjee's research focuses on the use of novel treatments and supportive care to improve outcomes in hematologic malignancies.

Kelly Brassil, PhD, RN, FAAN, is an Advanced Practice Nurse and the Lead Care Manager of Patient Access Support Services at The University of Texas MD Anderson Cancer. She has been named an American Academy of Nursing 2020 fellow. Her research experience includes studying patient-reported outcomes for patients with acute and chronic leukemia, breast cancer, and prostate cancer.

For More Information

Banerjee R, Lazar AA, Ryan C, et al (2021). Randomized study of digital life coaching during autologous stem cell transplantation [oral presentation]. Presented at: 63rd American Society of Hematology Annual Meeting & Exposition. Abstract 4023.

Granell M, Senín A, Barata A, et al (2021). Predictors of return to work after autologous stem cell transplantation in patients with multiple myeloma. Bone Marrow Transplant, 56(12):2904-2910. DOI:10.1038/s41409-021-01429-0

Banerjee R, Huang CY, Dunn L, et al (2021). Feasibility of digital life coaching during stem cell transplantation for multiple myeloma. J Clin Oncol (ASCO Annual Meeting Abstracts), 39(suppl_15). Abstract e24103. DOI:10.1200/JCO.2021.39.15_suppl.e24103

Transcript edited for clarity. Any views expressed above the speaker's own and do not necessarily reflect those of Oncology Data Advisor.