Listen to Jesus G. Berdeja, MD, and Ajai Chari, MD, as they discuss health disparities and equitable care strategies in multiple myeloma, including treatment for underserved populations and keys for everyday practice.
In this podcast episode, Jesus G. Berdeja, MD, and Ajai Chari, MD, discuss health disparities and equitable care strategies in multiple myeloma, including:
Presenters:
Jesus G. Berdeja, MD
Director of Myeloma Research
Greco-Hainsworth Centers for Research
Partner
Tennessee Oncology
Nashville, Tennessee
Ajai Chari, MD
Professor of Clinical Medicine
Director of Multiple Myeloma Program
UCSF Helen Diller Family Comprehensive Cancer Center
University of California, San Francisco (UCSF) Medical Center
San Francisco, California
Content based on an online CME program supported by an educational grant from GSK.
Link to full program:
https://bit.ly/3TZSmuf
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This transcript was automatically generated from the audio recording and may contain inaccuracies, including errors or typographical mistakes.
Dr. Jesus Berdeja (Greco‑Hainsworth Centers for Research, Tennessee Oncology): My name is Jesus Berdeja. I am the Director of Myeloma Research at the Greco‑Hainsworth Centers for Research at Tennessee Oncology. I am joined by my colleague, Dr. Ajai Chari.
Dr. Ajai Chari (University of California, San Francisco): Hi, Jesus. Pleasure to be here with you today. Ajai Chari. I am the Director of the Myeloma Program at University of California, San Francisco. Today, we will be talking about health disparities. Jesus, I think there is so much advancement in myeloma that we have seen, and it is really gratifying, but unfortunately, not everybody is benefiting. What have you noticed, and what are your thoughts on disparities in care in myeloma?
Dr. Berdeja: I think what is interesting is when we talk about disparities, we have, based on the history of clinical trials and healthcare, we immediately start thinking about race and ethnicity, which still remains a huge challenge in terms of access to care. Increasingly, we are starting to see more and more that there is more to that there are other things like socioeconomic status, healthcare literacy that are really starting to impact the likelihood that a patient is going to get some of these therapies that are working wonders for our patients these days. What do you think about that, or what have you noticed?
Dr. Chari: I think recently we have had some FDA scrutiny, appropriately so, on randomized phase III studies where we had a positive result. However, the representation of American patients was quite low, and specifically, African American patients. There is really this push to increase the representation of all patients in clinical trials, because clinical trials are meant for cherry‑picked patients, of course, that have perfect organ function, that are meant to show the efficacy and safety profile of a drug. Included in that should be the patients that we are seeing in the real world. Folks that are underrepresented in clinical trials, in addition to African Americans, would be frail, elderly, persistent renal failure, cytopenias.
We now know that cytopenias also is linked to race in the sense of Duffy‑null status. Patients with African ancestry will have a lower neutrophil count, which is clinically not significant. Yet, if we have cut points for study eligibility with higher neutrophils, we are excluding unnecessarily patients. I think part of this is the study population.
The other part, I would say, is some of these same groups are really not even getting to academia. We know in recent data that patients who have contact with an NCI‑designated comprehensive cancer center, it is an independent prognostic factor for better overall survival, but not everybody can come to an academic center. In addition to the groups that you highlighted, in Northern California, we have very rural parts of the state that do not have a lot of cancer care. We need to use video visits, and also get these patients to try to be working in partnership.
Those are some of the things that I have seen. I will say one strategy, as I alluded to, is really harnessing video visits to try to expand the connection between academia and community. Any other strategies that you think we should be thinking about?
Dr. Berdeja: Before I go to any other strategies, my God, you made so many points that I completely agree with. I want to expand just a little bit on some of them. I think you are right. One of the things that is very interesting to me when I first joined Tennessee Oncology and the idea of taking clinical research to the community, the whole idea was to try and reach those patients that could not get to the big academic centers. Also, to try and really get these novel therapies to the practitioners and the patients to have some experience in a more controlled setting so that when the drugs get approved it was easier to implement them. Part of what you said about the limits of the clinical trial eligibility, I think, really backfire on that approach because what is happening is those patients in the real world that do not meet all those very strict eligibility no longer are then evaluated on the trial. There are no strategies to help how do we how do we treat a patient with the phenol that we know is going to have more neutropenia with the new cell model, for example? Is that just as dangerous as someone who does not have the phenol? Because it may not be. The numbers are not the same. Neither us as investigators nor the practitioners in the world or the patient really benefit from excluding all those patients.
I think all those strategies that hopefully will start to be implemented to help expand access will help all of us, not just some of those subset of patients that are currently not being addressed.
The other thing, actually, I want to touch on, and I am curious what you think about was you brought up an excellent point that I think a lot of our new therapies are being approved based on randomized phase III trials, as they should be, but as you said, it is very difficult to get U.S. patients onto some of these phase III trials because some of the control arms are felt to be inferior or no longer the standard of care. You are right, the FDA is pushing significantly on that. I am curious as to how do we rectify that? How do you see that changing to ensure that we participate in these trials as well?
Dr. Chari: I can think of a recent CAR T clinical trial where patients were randomized to CAR T or a very good control arm that wasCD38 + carfilzomib + dexamethasone. In this moment in time, that is a great control arm. One caveat I will make is sometimes clinical trials are criticized for the control arm, but we have to keep in mind we cannot use the retrospective scope. Like when these studies were designed, which is potentially a year to three years, the regimens that are getting approved now were not available then, so if we are always criticizing every phase III study, we will never win and advance the field. It is just what was the best control arm at the time the study was designed, is really the question, how it should be asked. Ideally, you want to be a little bit of forward‑thinking because if you know something's about to imminently approve.
The problem with the regimen that I mentioned is, again, I had several patients that were interested and willing to participate and willing to be randomized, but are they going to trek all the way down to an academic center that is three hours away, when they can get that same regimen outside their door? This is what distinguishes U.S. with its geography from a lot of our other colleagues in Europe, for example, where the countries are much smaller, and the patients do not have to go such long distances.
I think one of the things we need to work on as a community is to improve ‑ and you have done a lot of this, and you can share your experiences. I would love to hear that. Can you enroll a patient but they get their standard of care therapy locally? Which means that the lab has to be certified, the pharmacy has to be certified, the physician has to be certified. There is a lot of vetting that needs to be done. I think that is a complicated issue.
Several other things that came to mind with the disparities work, we should highlight that probably some data suggests 40 to 50% of real‑world patients are actually not eligible for studies. When we have these big data gaps, we need to figure out.
One of my other pet peeves is that the way oncology drug design is done is that to get an accelerated approval in an unmet need, you need to get a response rate. To get that response rate, you push the dose to get that optimal response rate, but then there is no thought given to, is that dose actually deliverable in the real world? Then we end up having to step back and figure that out. We got to make it patient‑friendly. Now, the FDA is appropriately pushing back on the single‑arm phase II studies and forcing randomized dosing strategies so that we can really pick the best regimen. That is another good way of improving the field.
Another barrier which we need to address to getting these approved regimens in the real world is the REMS program. A lot of these new therapies like bispecifics and CAR Ts, which are off the shelf and should be in the community, but because they have a REMS program, many docs who maybe treat one to three myeloma patients a year may not be as excited about doing that, but it is important that everybody does these because the very patients that benefit from off the shelf therapies are these patients that we have been talking about that are excluded from the clinical trials. Curious to hear your thoughts on that. Also, in particular, if you have had any thoughts on the VA system, which is fascinating. We will go to the ‑
Dr. Berdeja: I know this is one of your pet peeves, and most of us is this whole REMS thing. The thing about REMS with things like bispecifics, for example, is that the REMS is really based on cytokine release syndrome and ICANS, which, as you know, only happens during the step‑up dosing. Maybe the first dosing. Never really happens after that, or the incidence is so infinitesimal that it should not be a requirement for someone who is just going to take the patient over after that step‑up, and yet it is required for something that they may never see. Now, it is one thing, obviously, if you plan to do the whole treatment, yes, that is what it takes; that is one thing. It has always struck me that the REM system is so inflexible.
Dr. Chari: Histologically discriminates, right? Because only myeloma bispecifics have REMS; lymphomas do not.
Dr. Berdeja: I was trying to get you to say that. I knew it would come up. We are running out of time here soon. You mentioned something that I just want to touch on, was the whole telehealth and how do we expand access to patients who cannot come to us. That is one way. One of the things that... Again, there are a lot of difficulties with trying to do this from a standpoint of separate centers in one place and then the local site being completely separate from the center, where there are some rational ways to try and do this.
Remember, there are very large practices in the U.S., and I would venture to say that the majority of patients taking care in the community probably belong to these large networks of private practices that should be able to operationalize this whole idea of having ‑ if they are going to have like a spoke and wheel model where you have centers that are more sophisticated, and then the other centers are where the patients are more further away, there is a way to potentially see the patient, put him on a clinical trial or start a treatment that may be logistically difficult, but then when they go back to their clinic, there is no reason why that patient cannot continue to be followed there, continue to do a telemedicine visit with the primary center to help the local doctor and the local patient oversee and anticipate some potential issues, and continue to basically handhold as needed those patients.
We are starting to do something like that. It has been really welcomed by patients. They really like the idea that they can go to the local clinic, be assessed by their APP, by the nurses, get laboratories, and then do a telemedicine visit with me three hours away, and tell them that they are on their bispecific, they are doing fantastic, I think we need to de‑escalate the frequency of therapy, and then I can reach out to their doctor and have them do that. Things like that will eventually become more commonplace, which would definitely help.
Dr. Chari: One hopeful note, maybe to conclude this segment, would be the population. We know sometimes African Americans are not only underrepresented in clinical trials, but their outcomes are sometimes inferior to non‑African American patients. The Veterans system, which normalizes the access, you do not see that disparity. It is a good example of how, when we give everybody the same care, we see the same outcomes. It is really important to get these amazing products.
To summarize this segment, some of the disparities that we have seen are the race, frail, elderly, poor health literacy, rural patients. We need to try to expand access, perhaps by telehealth, taking advantage of hub‑and‑spoke models, and increasing representation of these patients by increasing the eligibility permissiveness of these phase III clinical trials, and then we can get everybody these amazing products.
Dr. Berdeja: I could not agree more. Thank you. That was excellent.