Myeloma Management & Navigating Regional Oncology

Podcast Transcript

Dale Shepard, MD, PhD: Cancer Advances, a Cleveland Clinic podcast for medical professionals. Exploring the latest innovative research and clinical advances in the field of oncology. Thank you for joining us for another episode of Cancer Advances. I'm your host, Dr. Dale Shephard, a medical oncologist here at Cleveland Clinic overseeing our Taussig Phase I and Sarcoma programs. Today, I'm happy to be joined by Dr. Kasra Karamlou. Kasra is a medical oncologist with our Cleveland Clinic regional practice in Sandusky. He's here today to talk to me about management of myeloma. So, welcome, Kasra. Maybe to start, you can tell me a little bit about your role at Cleveland Clinic.

Kasra Karamlou, MD: Thank you, Dale, and I appreciate being on. I'm one of the staff physicians in one of the regional sites in the Cleveland Clinic Taussig Cancer Institute and our standalone cancer center is located in Sandusky, Ohio. We're an independent cancer center in the region here, but obviously we're a part of the greater Cleveland Clinic Cancer Institute and we collaborate with the Main Campus Cancer Institute very closely, as well as some of the other programs that are not necessarily with Taussig, but part of the Cleveland Clinic. So, we're very fortunate to have access to very, very high level care for our patients locally here at Sandusky, in the region.

Dale Shepard, MD, PhD: So, I know one of your clinical interests is multiple myeloma. Maybe just to start, what are the things that excite you about newer therapies in myeloma?

Kasra Karamlou, MD: I think, and as the audience knows, the treatment of myeloma has certainly changed and there doesn't go a month without another advance that happens in myeloma or there's an approval for a management of patients with myeloma. I think that the number of therapeutic avenues that have really become available in myeloma in the recent years has really expanded what we can do for our patients and what we can offer for our patients. And as we also do in the Cleveland Clinic, there's a number of novel clinical trials and combination of these agents, both in the terms of immunotherapy and non-immunotherapy based therapies that we're very, very excited about. So, I think that the way that the field is moving in myeloma is quite rapid. Sometimes when you're out in practice on a daily basis, it's difficult to keep up with the pace of that advance. And I think that's what really keeps it exciting as far as managing patients with myeloma and being in the forefront of treating this disease.

Dale Shepard, MD, PhD: So, what's typical in terms of, as a regional oncologist who sees many, many things, as patients come in with myeloma, what would be typical terms of where they are with their workup? Do you normally get them right out of the gate from primary care or have they usually done a lot of the workup or what does that look like?

Kasra Karamlou, MD: So, actually a lot of our patients that we do see with myeloma, a lot of them are newly diagnosed patients that are referred to us generally by either the local physicians or they're admitted to the local hospitals here, either for a different reason. And we are essentially the primary folks who essentially diagnose the myeloma and really start managing that from day one. So, it's very different obviously than what can be seen on Main Campus where obviously there's a lot of referrals for our patients who've been on previous therapies before. We tend to see a lot of patients who come to us, never been diagnosed with myeloma, and we make that diagnosis here in the clinic. A lot of these patients could be referred for either pain, or an abnormal MRI, or as a workup of anemia, or as part of a renal insufficiency workup, that we end up seeing them and diagnosing them with myeloma.

Dale Shepard, MD, PhD: Really you're seeing them, as you say, from the initial diagnosis and making those first treatment plans. Do you guys work with Main Campus, like in a Tumor Board style fashion, or how do you guys come across the initial therapy decisions?

Kasra Karamlou, MD: So, I think being part of the clinic gives us the ability to actually be involved in the Myeloma Tumor Boards directly with the folks Downtown and the Main Campus, which is obviously a tremendous advantage that we have being a regional site of Cleveland Clinic. And essentially, almost all of our patients who are diagnosed with myeloma or patients who may require a change of therapy, we have been routinely presenting those patients at the Myeloma Tumor Board, where obviously there is a consensus and as far as the management is concerned, and then we'll start treating those patients based on the consensus of the conference.

And obviously if there are clinical trials that the patient potentially could either qualify for, either here locally as part of the Cleveland Clinic Regional Research Program or potential protocols that may just be available at the Main Campus. That decision is made at that time and we make the appropriate referral. And obviously, if we feel that the patient is transplant eligible, that's another avenue where during that Tumor Board Conference, that decision is made. And then after several rounds of induction therapy, appropriate referral's made to the transplant program. So, it actually works very well in a sense that yes, we are not on the Main Campus, but we feel very close and I feel that our patients are getting that high level of care being part of this program.

Dale Shepard, MD, PhD: So, geographically you're roughly a couple hours away.

Kasra Karamlou, MD: So yeah, roughly about from the Main Campus, we're close to anywhere between 60 to 70 miles away, but we do have a pretty big regional area where we cover, so we can get potentially patients that are even further away from where we are. So, it really allows some of the folks who don't necessarily have access to a tertiary care center close by to them, be able to get that level of care or be directed to that level of care, close to home.

Dale Shepard, MD, PhD: And of course, when we think about transplants, which requires treatment on Main Campus, that becomes more of an issue. And do you think patients are typically pretty amenable to that?

Kasra Karamlou, MD: I think obviously, once we made that determination that the patient is eligible for transplant, I think most patients are amenable to that and they understand that that's an important part of their care. And we do also have fair amount of resources available to us being part of the Cleveland Clinic, which we could offer the patients. So, the patients can get down to the Main Campus for their consultation or even travel, a help that we can provide for them as part of what we can offer the patients, which also makes it somewhat easier for some of the patients that otherwise may have had a challenge getting Downtown.

Dale Shepard, MD, PhD: Well, I know I'm tremendously grateful for the work you guys do out in the region, in terms of being able to provide continuity of care and treatment to patients that we're co-managing and that really works out well.

Kasra Karamlou, MD: It really does work out very, very well, and we're really fortunate to be able to have access to the high level of care that's provided by you guys downtown here locally.

Dale Shepard, MD, PhD: So, oftentimes, I suspect that ... You did mention a wider reach even in the region for some of these patients with tumors and cancers that may not be as common. COVID has certainly been a huge impact on how we treat patients and virtual visits and things like that. How has that impacted how you're treating patients out in the region?

Kasra Karamlou, MD: Well, I think initially, as it was true probably with everybody, there was a learning curve as to how we're going to approach this. I think majority of our patients here locally really rather come and see the doctor personally, and obviously we've had certain guidelines that we've put in place and almost all patients follow those, and that have worked very, very well. And obviously, those are clinic-wide guidelines that are instituted here at our local clinic. But there are a few patients that potentially are further out that end up doing virtual visits and that has also worked well for us. One thing that we did notice is that there were some patients that were getting their therapies Downtown, either chemotherapy or potentially sometimes radiation therapy. And initially we did see a big influx of those patients not wanting to go down to the Main Campus.

And we saw a lot of those patients coming and seeing us either for their therapies, their injections, or radiation therapy, because of the fact that we are part of the Cleveland Clinic and we were close to their house. And we did see a big influx initially of that and I think some of that still continues. And that's, I think an advantage for the program as a whole, because we're still able to provide a care that's directed by experts like yourself Downtown, close by, and the patients are less exposed going back and forth or traveling.

Dale Shepard, MD, PhD: So, continuity certainly plays a huge role, and you talked about group decision-making between region and Downtown. And I think from the very beginning, it seems as though myeloma was really leading the charge in terms of care paths. And really, anytime someone walks into a Cleveland Clinic facility, they're getting Cleveland Clinic care and it's very consistent among all of the groups. So, how do care paths and the written out algorithms, how does that influence how you interact with us on Main Campus and provide care? Can you maybe talk a little bit about the care path process?

Kasra Karamlou, MD: I think obviously, the care path process is a very helpful process for the region and I think it's a very helpful process for the whole enterprise as far as essentially providing a standardized care for all the patients that come through the system. And I think that it's obviously a pathway that's designed in a multi-expertise level by the experts. And they're essentially easily available to us to implement when we see a new patient or a patient with relapsed disease, or as far as follow-ups are concerned. And I think part of that care path also is our ability to be involved in the Tumor Board process very easily from the distance that we are and being able to incorporate those care paths as part of the Multidisciplinary Tumor Board in myeloma into our daily practice of managing these patients. So, I do really think that they do provide a strong framework for us to provide the best care for our patients, even though they may not be necessarily at the Main Campus, but they are rest assured that they are receiving that degree of high level care, close to home.

Dale Shepard, MD, PhD: Part of any care path and any treatment of patients that we see in our clinics really involves clinical trials as part of that care. How are you able to incorporate clinical trials into the treatment of myeloma out in the region, and either having a trial there at the region for patients to participate in, or the knowledge of what trials might be available? So, how do trials fit into your practice for myeloma?

Kasra Karamlou, MD: So, obviously trials as with other malignancies, and especially with myeloma, are a big part of our clinical practice. And we want to make sure that we're offering the appropriate patients, the appropriate clinical trial, as well. As you are well aware, in the regions we obviously are part of the Taussig Regional Cancer Research Program, and that's a program that's run regionally where the regional investigators meet on a regular basis. We go through various protocols on a regular basis and approve various protocols, which we feel meet the demands of our patients. So, we have those trials, which some are actually Cleveland Clinic initiated trials available here at the region.

And also, we have access and we have the ability to easily with the research staff that we have available in the region, in our offices, quickly screen patients for potential trials that are available Downtown, as well as the staff, the research staff has the ability to get into the protocols and do a thorough screening of the patients before we plan on saying that a trial that's not necessarily available here locally is available Downtown, and we will definitely refer the patient there for that particular trial. So, they do play a significant role in the daily management of our patients and having the ability to either have those trials opened locally through the Cleveland Clinic Regional Research Program is important to us. And obviously, there are certain protocols that are not open regionally and with the research staff that we have available, we can easily access those and screen patients and refer them for the appropriate clinical trial. So, they play a significant role in the management of the patients.

Dale Shepard, MD, PhD: And I think that's a really important point to get out is that even patients that get referred to you in the regional practice have good access to those clinical trials. So, sometimes it seems there's a perception that people have to make the trek to Downtown Cleveland, but it's important to have people realize that that's not the case.

Kasra Karamlou, MD: Absolutely. And you bring up a very good point because there are a lot of trials that are available at the regional research facilities of the Taussig Institute, and patients can access those trials easily here, locally close to where they live. So, that's very true, they don't have to make the travel all the time.

Dale Shepard, MD, PhD: So, I'm going to double back into your interest in myeloma and pick your brain a bit. As you see all the progress that has been made in this disease, what do you think is the most promising of the new therapies?

Kasra Karamlou, MD: I think there's obviously a lot of novel therapies that have been approved recently, which have been incorporated into a management of myeloma for us. I think, well, one area of excitement obviously is the role of immunotherapy in myeloma as it is across many of the other malignancies. But I think certainly in myeloma, there's been a wealth of data suggesting that immunotherapy has a significant role in management of patients with myeloma, either through monoclonal antibodies, which obviously have been approved now extensively in managing myeloma across multiple lines of therapy. And immunoconjugates, which also have started to play an important role in myeloma and exactly how those are delivered and other ways to stimulate the immune system, either with BiTE therapies and obviously CAR T therapies. Those are I think, areas of exciting avenues of advance in multiple myeloma. I think the CAR T therapies are going to be as significant in myeloma, exactly the target of those CAR T therapies, and we have the ability to have access to those therapies.

Allogeneic CAR T therapies, which are sort of off shelf CAR T therapies. We do have a clinical trial Downtown, which is looking at that, and I think that's another exciting area. And as I mentioned, the BiTE technology and BiTE therapy in myeloma, I think is another significantly important pathway in managing patients with myeloma. And also there are other novel mechanism of actions such as some of the other cell mods or immunomodulatory pathways, novel drugs that are becoming more available that are more potent, less toxic, in that realm. And also some of the other novel avenues such as XPO1 inhibitors and how we utilize that in myeloma. I think all of those are becoming quite interesting and hopefully we'll find a way and get into that algorithm of how to best manage these patients.

Dale Shepard, MD, PhD: So, lots and lots of progress, lots of new treatments. And with that comes the challenges I guess, of which patient is best to receive which therapy. Anything that's particularly interesting in terms of how do we get the right patient, the right therapy? So, within a disease state, how do we make those selections? How do we pick the right therapy for the right patient?

Kasra Karamlou, MD: And I think you bring up a tremendously important point, who should get what? And obviously, in the era of personalized medicine, we want to have the ability to really deliver pinpoint care to the appropriate patient. And obviously, in myeloma we're fortunate that we have so many options, but we still haven't quite figured out who should get what based on, for example, their molecular characteristics or other factors of their disease. I think that's an evolving area and I think as time goes by with the number of tools that we have available, I think that will become more clear. Obviously, I think that the standard therapy for standard risk patient has been our triplet therapies. Obviously, there's more interest nowadays with quadruplet therapies upfront, but we haven't been able to necessarily distinguish who gets what.

And obviously, we have that the high-risk patients and also the ultra high-risk patients, and right now there's not necessarily any randomized trials that can help guide us how to potentially manage those patients differently than our standard-risk patients. There's a number of trials ongoing that is addressing that. So, obviously that's an area of significant interest. And I think as far as another important factor in myeloma is really achieving the deepest response with minimal residual disease assessments and how that's assessed either through sequencing or through flow cytometry or with the addition of radiographic minimal residual disease. And we do know that patients that do achieve that tend to do better, so obviously that's another important goal of therapy. And as far as who should get what is concerned, we're still, I think, searching to look for markers, to try to define how we can achieve that end point of minimal residual disease in a particular patient, in the best manner. And I think that's where really, the treatments are headed.

Dale Shepard, MD, PhD: So, certainly that's going to be a challenge moving forward and we've made great progress in really all phases of treatment. But when you think about managing patients with initial diagnosis or relapse or a transplant setting, what's the biggest gap, where do we need to make the most progress? Where do we need to really spend our efforts and say, this is an area that we really got to do better?

Kasra Karamlou, MD: Well, I think in myeloma, obviously I think, well, one of our biggest area of needs I think is how to ultimately manage after risk stratifying our high-risk and ultra-risk patients. I think that's a big area of need in managing myeloma patients. And I think a lot of that really comes up front because I think as with many other malignancies, you're able to achieve your best remission, best potential duration of remission, and also possibility of cure with the most effective frontline regimen. Although, obviously our frontline regimens in myeloma have improved significantly, and based on your risk of disease, your remission duration will also be impacted by that. We have obviously some high-risk or ultra-high risk patients who still, despite our best therapies aren't doing well.

And I think that's a big area of need, how best we need to optimize management of those patients in the frontline setting, so we can have the ability for those patients to actually have a long, durable remission. And obviously, the other big area of needs is, despite the fact that we've had number of approved therapies in myeloma, unfortunately, patients do relapse and there is obviously more need for patients who are double IMiD refractory, or CD38 antibody refractory, and a double proteasome inhibitor refractory. And I think there's a lot of need for finding optimal therapies and optimal combinations for managing those patients as well.

Dale Shepard, MD, PhD: Well, Kasra, you've given us lots of great insight on coordination of care, on the issues related to treatment of myeloma. Do you have any additional comments?

Kasra Karamlou, MD: No. I just wanted to thank you very much for including me in this program. I think that we have a very successful program, which has worked very well in a sense of being a part of the Cleveland Clinic, but not necessarily being inside the Cleveland Clinic. I think we're able to deliver high level of care that is coordinated through the clinic, out to the region. And I think that provides a unique service that really serves the local communities exceptionally well.

Dale Shepard, MD, PhD: Well, thank you very much for all you do, and thank you for being with us today.

Kasra Karamlou, MD: Thank you very much.

Dale Shepard, MD, PhD: This concludes this episode of Cancer Advances. You will find additional podcast episodes on our website clevelandclinic.org/canceradvancespodcast. Subscribe to the podcast on iTunes, Google Play, Spotify, SoundCloud, or wherever you listen to podcasts. And don't forget you can access real-time updates from Cleveland Clinic's Cancer Center experts on our Consult QD website at consultqd.clevelandclinic.org/cancer. Thank you for listening, please join us again soon.