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BackTable / VI / Podcast / Transcript #522
Podcast Transcript: Advancements in Treatment of Metastatic Ocular Melanoma
with Dr. Altan Ahmed and Dr. Sid Padia
Is there a way to treat liver metastasis secondary to uveal melanoma without introducing systemic, treatment-related toxicity? Dr. Altan Ahmed (interventional radiologist at Moffitt Cancer Center) and Dr. Sid Padia (interventional radiologist at UCLA) join guest-host Dr. Kavi Krishnasamy to discuss HEPZATO, a novel device-based treatment for liver metastases from uveal melanoma. You can read the full transcript below and listen to this episode here on BackTable.com.
Table of Contents
(1) Percutaneous Hepatic Perfusion (PHP) for Liver-Metastatic Uveal Melanoma: HEPZATO
(2) Patient Selection Criteria for HEPZATO
(3) Interventional Workflow for Liver Metastases from Uveal Melanoma
(4) Team Coordination & Procedure Timing
(5) Intervention Availability for a Rare Tumor Patient Population
(6) Practical Considerations in HEPZATO Drug Dosing
(7) Optimizing Treatment Cycles & Patient Response
(8) Patient Post-Treatment Management & Adverse Effects
(9) Gaps in Current Intervention & Future Research
(10) New Applications for PHP Therapy
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[Dr. Venkatesh Krishnasamy]
Welcome to Backtable. We have two phenomenal guests today. Sid Padia, interventional radiologist at UCLA and Altan Ahmed, interventional radiologist at Moffitt Cancer Center. We're going to talk about HEPZATO today. Welcome to both my guests, both leaders of the interventional oncology space in the US. Thank you for being here.
[Dr. Siddharth Padia]
Thank you for having us.
[Dr. Altan Ahmed]
Thanks, Covey.
(1) Percutaneous Hepatic Perfusion (PHP) for Liver-Metastatic Uveal Melanoma: HEPZATO
[Dr. Venkatesh Krishnasamy]
All right. Let's get started. We're going to, like I said, talk about HEPZATO or CHEMOSAT as it's called in Europe. Tell me, Sid, what is HEPZATO? What is CHEMOSAT?
[Dr. Siddharth Padia]
HEPZATO, CHEMOSAT, generic name is PHP or Percutaneous Hepatic Perfusion. I would consider it relatively new in the US just because it got FDA approval last year and is a device related treatment for patients with liver metastases from uveal melanoma. It is a way to deliver high dose of chemotherapy into the liver.
In this case, the chemotherapy drug is called melphalan, which is a DNA alkylating agent. The device is designed for us to deliver this via the hepatic artery, just like we do many other hepatic artery procedures. The difference is that we are withdrawing the drug at the same time via the IVC, filtering the drug out through a filtration circuit, and then returning the filtered blood back in.
This whole device, including the drug, is called-- the trade name is HEPZATO kit in the US, which was FDA approved in 2023 for uveal melanoma metastases, and then became commercially available in 2024.
[Dr. Venkatesh Krishnasamy]
Got it. Probably to the average practitioner in the US, it sounds a little bit like a surgical hepatic pump, but this is obviously very different. How is it different?
[Dr. Siddharth Padia]
I think there's a couple of differences. Number one, when we talk about infusion pumps in surgery, which actually our group does a good number of them in the colorectal cancer setting, the difference is that the drug that we're using in this case, which is melphalan, is very cytotoxic, potentially, and especially in terms of bone marrow suppression.
The systemic dose needs to be minimized. The difference between a surgically implanted pump and this is-- the main difference is that we are withdrawing the drug after the first pass through the liver, and then filtering the drug out through this filtration circuit. That's number one. Number two, this is given all at once during a procedure.
Then what allows us to do this in IR appropriately is that we're able to repeat this down the line because this is all percutaneous. By percutaneous, meaning femoral artery, femoral vein access, things that IRs are very used to and very comfortable with for the last several decades. This allows us to repeat treatments for patients, which in the past, when this same procedure was done in the surgical setting, you really can't do this operatively multiple times.
[Dr. Venkatesh Krishnasamy]
Got it. No implanted device. Then multiple procedures, like you said, so big difference, and lends itself to our skill set, which is great. Altan, Moffitt has the longest running US experience for PHP or HEPZATO. We already talked a little bit about when it was FDA approved, but how long has the device been around? How long have you been using it at Moffitt to treat patients? Great question.
[Dr. Altan Ahmed]
Great question. Yes, we have about over a decade now, of experience with Percutaneous Hepatic Perfusion. The device itself, in one form or another, has been around since the early '90s, actually. First described in Japan and MD Anderson around the same time, early '90s, in animal models, and then '93, '94 is where the first human trials were conducted.
In some form, the double-balloon catheter for hepatic venous isolation has been around and evolved over time, not only the catheter itself, but also the filtration mechanisms with the carbon-based system. Really an evolution of a technology that's been around for quite some time. Then even before that, if you look at isolated hepatic perfusion that Sid had mentioned there, that has been described as far back as 1960.
An evolution of that, a surgical procedure that could only be performed once, great response rates, high morbidity. This is a natural evolution in something that can be repeated and continue to be efficacious for patients.
(2) Patient Selection Criteria for HEPZATO
[Dr. Venkatesh Krishnasamy]
Over that time, obviously, like all interventions, we evolve, our patient selection gets better. Tell me, how are you choosing your patients? ECOG, Child-Pugh, ALBI scores, give me some details.
[Dr. Altan Ahmed]
Overall, not very different from most of our other local regional therapies. Liver dominant disease number one from a tumor perspective, ideally less than 50% of the liver being involved. ECOG zero to one, we don't want major cirrhosis. Child-Pugh A, B and C would usually be excluded.
Baseline hepatic synthetic dysfunction would usually be an exclusion criteria for patients. Patients who cannot undergo general anesthesia, this is going to be one key difference from our other local regional therapies. This is a pretty intensive procedure for a patient, general anesthesia, perfusion bypass, all that. They have to be relatively healthy otherwise.
[Dr. Venkatesh Krishnasamy]
And cardiac strain. I think patients that have underlying cardiac morbidities, the blood pressure liabilities is there as well. What about things like-- you mentioned tumor burden. What about biliary incompetence, post-whipple, biliary stents, things like that? Those are areas where I will sway away from TACE and ablation, even with long-term antibiotics.
Then Sid and I recently had this conversation about radiation segmentectomy in this type of patient as well. How about that patient population here?
[Dr. Siddharth Padia]
Fortunately, it doesn't really happen that often. Most of these patients, keep in mind, we're talking about a very targeted group of people who have liver metastases from melanoma. These patients in general are not going to have prior biliary surgery. If they did, it's most likely going to be unrelated to their cancer and perhaps related to something else. We haven't really encountered that.
The trials, which we'll talk about later, did exclude those patients just because you want to optimize your safety during a trial. We don't really know what's going to happen the first time we have that scenario. I suspect it's going to be fine because we're not causing tissue necrosis. The challenge in doing radiation segmentectomy or thermal ablation or chemoembolization in the setting of prior biliary surgery is that you're leaving necrotic tissue behind when there's reflux of contents in the bile system. You're going to get that necrotic tissue infected.
This doesn't because any necrosis. I suspect, we would probably put them on antibiotics, but I suspect it's not going to be a big issue. We haven't had any experience with it. Altan, have you guys done any patients with biliary surgery?
[Dr. Altan Ahmed]
Like you mentioned, it would be a really infrequent situation for this specific patient population, but we haven't had that situation come up thus far, at least.
[Dr. Siddharth Padia]
There's definitely two differences between this population and other patients with liver metastases like, for example, colorectal cancer. Number one, these patients have-- 99% of them have not received cytotoxic chemotherapy in the past. Many of them have received immune checkpoint inhibitors, which is standard of care, but cytotoxic chemotherapy is not.
The nice thing is that they shouldn't have the vascular effects from chemotherapy. They shouldn't have chemotherapy-induced stay-out-of-hepatitis. Pretty much every patient I've seen has had absolutely normal hepatic function. In fact, if you see someone who does not have normal hepatic function, something else is going on, which needs to be investigated.
It's entirely possible they may have infiltrative tumor, which is going to because liver failure. The patients are pretty well set up for this procedure in that sense that I don't have to think about or deal with interactions with other chemo agents, at least at this time.
[Dr. Venkatesh Krishnasamy]
Great point. For both of you, I guess, if you do see a patient that's on systemic therapy, what are you saying? Ipinevo? Tibentifasp? Anything else?
[Dr. Siddharth Padia]
Those are probably the two most common. There's others. We have not discontinued their systemic therapy during the course of this treatment. To our knowledge, we haven't had any interactions or adverse interactions between the immune checkpoint inhibitors and this. There are ongoing trials. One is in Europe called the CHOPAN trial, looking at the combination of immune checkpoint inhibitors and cutaneous hepatic perfusion, which results will hopefully be out later in 2025.
[Dr. Venkatesh Krishnasamy]
Yes, I think we're all excited to see that. I think the phase 1B data came out last year at ASCO and they're hoping to publish a phase 2B data this year at ASCO, so that could be very impactful for this patient population. Altan, I want to go back to one thing real quick, talked a little bit about cardiac co-morbidities.
Your group recently published troponin leaks after PHP, if I'm not mistaken, showing no long-term consequences and them all being subclinical. Again, obviously, cardiac strain during the intervention, which we'll get to here shortly, can you tell me a little bit more about that?
[Dr. Altan Ahmed]
Sure. You'll often find troponin leaks in these patients if you're checking the labs afterwards. We found that, overall, if there's no other sign other than the biochemical finding that it's inconsequential for these patients. ICOs have not shown anything. Typically, you will see a little bit of troponin leak just from the stress induced by the procedure itself.
There's a lot of hemodynamic shifts, a lot of changes happening during the procedure. Not totally unexpected, but as long as you're selecting patients appropriately, you wouldn't expect to have any adverse effects long-term.
[Dr. Siddharth Padia]
Altan, what pre-op stuff are you guys doing in terms of cardiovascular testing beforehand?
[Dr. Altan Ahmed]
Typically, just ECHOs, yes.
[Dr. Siddharth Padia]
Yes, we were debating between just getting a resting ECHO and we decided to get a stress ECHO on everybody to, in theory, more simulate what they're going to undergo during a PHP. We've done that in every patient. It is not, at least where I live, it's not easy to get a stress ECHO. There's a wait time and so on.
Depending on where you are in the country or world, there can be logistic hurdles in getting a stress ECHO. You can always have the occasional false positive as well that you're going to have to go down that rabbit hole. It's by no means a perfect answer, but we've been doing that just in the interest of making sure that no one has an MI on the table because that would obviously ruin our program in the beginning.
(3) Interventional Workflow for Liver Metastases from Uveal Melanoma
[Dr. Venkatesh Krishnasamy]
Absolutely. For here, our practice has been resting for the most part, resting ECHO. Let's get into that a little bit, Sid. If you can, walk us through your workflow. We talked a little bit about the devices already that we're using. We talked a little bit about the drug, but walk us through the workflow, the day of, the procedure, a little bit of pre-post. What goes into the actual intervention?
[Dr. Siddharth Padia]
Beforehand, it's similar to other patients who undergo local regional therapy in that we do a consultation in advance, insurance pre-authorization. To be honest, the insurance pre-authorization has been fairly straightforward so far. The only real difference is that they undergo some cardiac testing.
In our case, a stress ECHO, but as Altan mentioned, in his case, a resting ECHO. That's the real one difference. We also have an anesthesia consultation, which is typically done virtual. Those are the two changes.
[Dr. Venkatesh Krishnasamy]
Real quick, are you getting an MR of the brain or a CT of the brain beforehand to look for intracranial metastases?
[Dr. Siddharth Padia]
We've debated. The reason to get an MR of the brain is to look for intracranial metastases. You do pretty heavy doses of anticoagulation during the procedure. We have not yet started routinely getting MRI brains. Part of it is a logistical issue. We have quite a bit of delay in getting outpatient MRs.
I try not to push the patients back too far. I don't think it's a bad idea. That being said, the incidence of brain metastases from uveal melanoma is pretty low. That being said, it's not zero. I think it's, at this point, probably operator choice whether to get one. Altan, are you guys getting brain MRIs on everybody?
[Dr. Altan Ahmed]
We are, yes.
[Dr. Siddharth Padia]
In terms of the day of the procedure, in the morning, it's pretty much the same as anyone else getting any local regional therapy. Once we put them under general anesthesia, the main difference is we do get a Foley catheter, they're getting a radial arterial line, and we put in a standard triple lumen central venous catheter, and that's really for blood draws during the procedure and to give intravenous vasopressors.
[Dr. Venkatesh Krishnasamy]
You mentioned earlier, arterial access, venous access, arterial access is standard five, six French, venous access is how big, and what do you put through that venous access?
[Dr. Siddharth Padia]
It's interesting, Altan had talked about the fact that Moffitt's been doing this for over 10 years. I think what's evolved over 10 years and what now really belongs in the IR alley is over the last 10 years, I think two big things have happened in our profession. Number one, we started working with anesthesia more and more often.
I think when I started practice in 2009, getting an anesthesiologist in the IR suite took a lot of effort. Nowadays, they're there all the time, so they're comfortable with it. Number two is working with large board devices, specifically in the venous space. Now that we're doing so much DVT and PE work, putting in a 24 Fr sheath in the right femoral vein where I thought 10 years ago would've been insane is now fairly common in our practice.
When we talk about the access sites, we're really talking about a five or six Fr femoral arterial sheath, that's standard, that we do five times a day, an 18 Fr femoral venous sheath, and a 10 Fr right internal jugular sheath. These are all pretty standard and routine accesses that all IRs, I think, are proficient at performing.
In terms of the catheterization, it's relatively straightforward. I think from a technical perspective, if you, for example, can do chemoembolization or radioembolization, this is really nothing that you can't do.
[Dr. Venkatesh Krishnasamy]
I would argue, and both of you, please feel free to disagree with me, on the arterial side, it's a base catheter, it's a micro catheter, you're parking usually right, left, relatively low bar type distribution. It's not a lot of complex arterial catheterization and then infusing from there. On the venous side, it's that double balloon catheter.
The top balloon is at the caviatorial junction, bottom balloon is below the accessory hepatic veins, and you're literally isolating the liver as a circuit, which is one of the things that's most fascinating about this intervention to me, but tell me more.
[Dr. Siddharth Padia]
We've been doing low bar treatments, and by low bar, right hepatic artery, middle, left, et cetera, in every patient, and then effectively treating the whole liver in every case. Altan, are you guys doing the same thing?
[Dr. Altan Ahmed]
We are, absolutely. We're treating the whole liver.
[Dr. Siddharth Padia]
Are you doing any segmental treatments? Because we have not been. It doesn't really make, for us at least, a whole lot of logical sense to start doing PHP segmentectomies and so on.
[Dr. Altan Ahmed]
No, we're not there yet. We're also in the low bar space.
[Dr. Siddharth Padia]
Covey, as you said, the catheterization itself, let's say compared to an average Y90, is probably going to be, on average, either the same or a little bit easier.
[Dr. Venkatesh Krishnasamy]
We're isolating the liver with that double balloon catheter. Two large bore or large balloons, 18 Fr catheter. Then, Altan, you mentioned the veno-veno bypass circuit already with the filtration. Tell me a little bit more about that and how that works.
[Dr. Altan Ahmed]
Sure, absolutely. As you mentioned, the catheter itself has an excephalide balloon, cranial, or a caudal balloon. The cranial balloon is wedged at the inferior cavoatrial junction until it gets inflated and then retracted until it seems like an acorn-type shape. Wedged into that junction, the inferior balloon is inflated until it flattens around the edge of the IBC.
To confirm that we have isolated that segment, we actually take the patient's off pump momentarily and do a venogram to make sure we have stasis of contrast within those two balloons and no leak, most importantly, a cranial leak that would go into the right atrium. Once we do that, the patient is basically brought online for the filters, the charcoal filters sequentially, which are arranged in parallel.
We put those in, and then ultimately, once the hemodynamics have stabilized, you clamp the bypass line. I should say that when we put the balloon catheter in, before we inflate, the patient is put on the pump and the circuit is started before any of that happens.
(4) Team Coordination & Procedure Timing
[Dr. Venkatesh Krishnasamy]
Obviously, as we mentioned already, there's a lot of cardiac and blood pressure lability here during the intervention. What are the points-- I mean, you have an anesthesiology team in the room, you have a perfusion team in the room, and that's the IR team. What are the-- or IR or, plus surgical oncology, every center I think is a little bit different.
What are the points where you're really communicating about, well, the blood pressure is going to change here, we need to be on the same page? What are those points during the intervention?
[Dr. Siddharth Padia]
The one thing to keep in mind is that you have-- your anesthesiologists at any center are going to be trained. They're going to go observe a patient getting treated at another site and then they get proctored. They're not walking into this new. Our anesthesiologists, I think, actually went to Altan's Center at Moffitt and watched him and our lead nurse and our lead tech also went there as well.
They learned from Altan's group, our anesthesiologists learned from them, they brought it over. Then they knew what to expect and then they got proctored as well. Their first case, an anesthesiologist came in and watched them do it. There is a little bit of prep and we have right now three anesthesiologists who are signed off to do this.
It's not our entire, 150 anesthesia faculty group that does this, the doc of the day. I personally think-- there was always discussion when this started, do you need a cardiovascular or a cardiac anesthesiologist? I don't think we do. Even though that we're using a bypass circuit, there are certain key points where the blood pressure will drop, number one, when you inflate the balloons. Number two, when you hook up to the filter.
As long as the anesthesiologist is prepared for it and you work together, it's honestly nothing that they can't handle.
[Dr. Venkatesh Krishnasamy]
Great point. Going back to what you said earlier, all three teams not only have to go observe a case, but then have to be proctored for their first case. I think that's an FDA mandate. That's anesthesia, that's perfusion, and then the interventional team, whether that's IR alone or IR plus surgical oncology, depending on what center you're at.
That's a great point as well. A couple of key points during the intervention where the blood pressure will drop, anesthesia is on alert to push the blood pressure with some pressors. Learned that over time, that flooding with a lot of fluids just overloads the patient afterwards as well. Optimizing the blood pressure, preventing vasospasm so we can deliver the drug. How long does this all take? This is a long process.? How long does this all take?
[Dr. Siddharth Padia]
Are you asking about our first patient or the most recent patient? Because there's definitely a learning curve.
[Dr. Venkatesh Krishnasamy]
Absolutely. That's a great point. Your first case, and Altan, it's been several years for you, but if you remember, how long was the first case and where are you now?
[Dr. Altan Ahmed]
That's a good question. Overall, I would say on average, you'd anticipate about three to four hours. Now your first cases might be closer to five hours, just depending on logistics. There's a lot of different teams involved here. Now, as you mentioned, each center is going to be a little bit different.
At Moffitt, we do work hand in hand with our surgical oncology colleagues. It's actually a surgical oncologist, an interventional radiologist, the profusion team, anesthesia, and then pharmacy. That's another big key that we have there. You have to be in very close communication with the pharmacy.
We are actually requesting the drug to be reconstituted at a specific time so that we are not wasting time and it doesn't start to degrade. All of these things add to the time needed for the procedure. If, by chance you happen to order the drug sooner than you are ready and end up waiting too long, you may have to get more drug later on, which can extend the time for a procedure.
[Dr. Siddharth Padia]
I would say that our first procedure took about three and a half to four hours. Now, our last several, and I'm talking about the IR procedure time, not including the anesthesia setup time and anesthesia breakdown time, is about two and a half. It is actually quite manageable. Part of it, as Altan mentioned, is coordinating with pharmacy.
The way it works is that the drug comes in a powder. It cannot be prepared the night before or so on, because once it is prepped by the pharmacy, meaning made into a solution, it has an expiration. That expiration, I think, is around 60 minutes. You need to really get it into the patient within that 60 minute window.
That includes, them delivering it, delivering to the IR suite, hooking it up, et cetera. Then, for example, if you're going right, middle, and left hepatic arteries, you got to do all three hepatic arteries within that 60 minutes. You can't just have the drug sitting in the room and then start your procedure.
You want to time it appropriately. At the same time, you don't want to ask for the drug at the very last minute and then sitting around for 30 minutes while they're mixing the drug and the patient is on these filters, hypo-- relatively hypotensive, or at least on high dose vasopressors at the same time.
A large part of this learning curve was trying to time everybody in order to minimize your downtime and to minimize any degradation time of your drug. We figured out a pattern where it worked well for us. Lately, I would say our procedure time, the IR procedure time is about two hours, 30 minutes.
[Dr. Venkatesh Krishnasamy]
That's fantastic. For me, that's a complicated three, four dose, Y90 delivery, trying to move my catheters around in different places in a patient that can't get sedation. That's pretty amazing. What about you, Altan? Where are you at today?
[Dr. Altan Ahmed]
Around the same thing, two and a half hours for the IR time. Obviously, getting the patient back there adds total room time to closer to four hours. As Sid mentioned, I think it's a really important point, your balance is minimizing the pump time and maximizing the amount of time you have for the drug to be most active.
[Dr. Venkatesh Krishnasamy]
Great point. As you said, 60 minute time before drug expiration. You have to get the drug in. You're having anesthesia, monitoring the blood pressure and optimizing the blood pressure. You're not getting a lot of vasospasm. You're not getting reflux of the drug. At the same time, Altan, you alluded to it, there's some data out of Europe that the longer you're on filter without delivering the drug, there is some degradation of the filter and you're extracting less drug.
Important to time going on filtration at the right time and then immediately start giving the drug, correct?
[Dr. Altan Ahmed]
Absolutely. The filters lose efficiency over time. The longer you're pushing blood through it, the less efficient you're getting at extracting that drug and the more possible systemic exposure you're going to have to deal with on the tail end of this procedure. The other part of this is, just pump time in general also is associated with increased morbidity after the procedure as well, the thrombotic events and whatnot.
[Dr. Siddharth Padia]
These things all take practice. In the beginning, the coordination's not perfect. One of the things I've noticed not only in our center and other centers, when you're starting out, you don't know how long your pharmacy is going to take because beforehand, when you have your meetings with them, they're going to say, okay, it's going to take 20 minutes.
Then in reality, it's not 20 minutes. You find out, oh, your pharmacy is not three minute walk. It's really an eight minute walk. Then after a little bit of practice, you're like, okay, now I know that as soon as I get my reverse curve catheter in the celiac artery, I can call for pharmacy because I know that's how long it's going to take for me to get catheterization of all the hepatic arteries and put the double balloon catheter up and then hook up to the filter.
It'll take me about 20 to 25 minutes to do all that work. Now I can time it appropriately.
[Dr. Altan Ahmed]
Exactly, and each practice is going to identify those little time points that fit for them based on pharmacy location, pharmacy time, turnaround time, and all that stuff.
[Dr. Siddharth Padia]
One of the interesting, from just a practice standpoint, not a medical standpoint of having done, all of us have done a lot of oncology practice and then we have a huge venous practice. One of the differences of this procedure compared to others is the amount of coordination you have to do.
It's not the technical challenge. The amount of coordination you have to do has been both highly challenging and highly gratifying. You work with groups that you're not used to working with like groups like perfusion and specific anesthesiologists. It's nice to develop relationships with these people.
We developed a great deal of cohesion. We figured out ways to just improve our practice in general. There's been a lot of positives that have come out of starting this practice.
(5) Intervention Availability for a Rare Tumor Patient Population
[Dr. Venkatesh Krishnasamy]
Just the patient population, right? This is a rare tumor patient population. They don't have a lot of options. This is a pretty amazing interventional solution that we can now offer them. I think that's also super gratifying on our end as well. That we could offer this to the patients.
[Dr. Siddharth Padia]
Yes, it's interesting. These patients are very different than other people with hepatic metastases for several reasons. Number one, when you look at their prognosis, even with the standard currently available systemic therapies, it's pretty poor. Tibentifus, which is one of the immune checkpoint inhibitors, but it's really only valid for about 40% of patients with a specific HLA subtype is quite effective.
Once they fail that, there's not really a great second line. If you're not a candidate for Tibentifus, you're talking about the standard Nivolumab and Ipilimumab, also relatively low response rates and not a great deal of survival. There's other trials of other systemic agents, obviously in the pipeline. Overall, this is not a-- let's say, if you compare it to breast cancer, which there are, I don't know, 20 different lines of systemic therapy that I think most IRs, it's way beyond our real deep understanding.
This is relatively wide open. There's not a lot of options for patients. It's nice that this came out where this has the potential to treat a very heavily needed patient population. It does not have, as far as we can tell, any adverse interaction with the currently available therapies. I think the one difference from a practice standpoint, uveal melanoma, we're not talking about cutaneous melanoma, uveal melanoma is relatively uncommon.
If you're thinking about starting this in your own hospital, you really have to look at, do I have this patient population? Am I going to be seeing one patient a year? Because if you are, it's really not worth the effort to start a program like this. Both Altan and I happen to work at places which have a big uveal melanoma population because we have either surgeons or medical oncologists or ophthalmologists who really focus and specialize in this.
For example, in our case, we have people drawn from pretty much the entire West Coast who see our one ophthalmologist, Tara McCannell, and that's all she does is uveal melanoma. Because of that, we have this pipeline of patients that get funneled into UCLA from pretty much the entire Pacific time zone.
[Dr. Venkatesh Krishnasamy]
I suspect that that's probably happening across the country. Regional referral centers for uveal melanoma, as you already alluded to, whether it's Jefferson in Philadelphia, Altan in Moffitt, we're starting a program in the South, I'm at University of Alabama, Birmingham. You have these pockets of patients and they can go.
Then as you already alluded to, there is an experience standpoint portion to this. We've learned that from every other intervention. The more experience these individual centers have, the better off their patients do, correct?
[Dr. Siddharth Padia]
Yes, it's never going to be like the way thermal ablation or radio embolization or chemo embolization is practiced now in the United States where I live in West Los Angeles, if I were to make a 10 mile radius from my hospital, there's probably eight or nine other centers that do radio embolization.
That's not going to happen with this therapy. Even in Los Angeles County of 10 million people, there's probably at the end of the day, maybe going to be two, maybe three, but probably two centers that perform HEPZATO for this population. Altan, I can't imagine there's going to be another center in Tampa that's going to be doing HEPZATO.
[Dr. Altan Ahmed]
Highly unlikely. As you said, it's going to be set up more as a regional referral type practice, which I think it's great. You want to have expertise in what you're doing and offering these patients.
[Dr. Siddharth Padia]
Keep in mind, that also means that it doesn't necessarily have to be in this ivory tower quaternary care center either. There are other places that are-- there are private practice places, Honor Health in Arizona, a private practice hospital that's doing very high quality work that is doing HEPZATO procedures.
It doesn't necessarily have to be, you need to be in these ivory tower academic centers. I don't personally think that's the requirement. I think the biggest requirement is that you have to have the patient population to treat.
[Dr. Altan Ahmed]
I agree.
(6) Practical Considerations in HEPZATO Drug Dosing
[Dr. Venkatesh Krishnasamy]
That's a great point. Sid, going back to what you mentioned about thermal ablation and Y90, I think that's a great segue. Altan, the drug dosing is part of this as well. In the FOCUS trial, which is a landmark trial that got HEPZATO FDA approval, it was just a flat dose above a certain body weight.
Tell me a little bit more about the drug dosing. Do you ever dose reduce in certain situations in these patients? I know that's a little bit of a loaded question because we don't know the answer to that probably at this point. Then is there going to be a role in the future to as opposed to just dividing the dose between right and left liver dosing to tumor burden as we do with Y90?
[Dr. Altan Ahmed]
Great and very important question. Yes, there is a dose that came out of the phase one trial at the NIH back in 2005. That dose was three milligrams per kilogram for ideal body weight. Now they tested anywhere from 2 to 3.5 and 3.5 is where they had the most adverse events.
Three was selected as the dose to a maximum of 220 milligrams. Ideal body weight is the key thing here. Now, when we do dose reduce, there are instances where that is done typically in patients who have adverse events, mainly neutropenia. Delayed recovery in between treatments or they have neutropenia leading to an infection or something like that or fibromyalgia neutropenia.
If they have delayed recovery over six to eight weeks for their white counts to bounce back or recover, then we would consider that patient for a 2.5 milligram per kilogram dose versus the standard three. Sid, I'd like to definitely hear what your practices have been so far.
[Dr. Siddharth Padia]
Thanks for the recommendation on that. I appreciate it because right now in my opinion, the dosing is terrible, to be honest, but that also means it leaves a lot of room for improvement and optimization. As Altan mentioned, it's 3 milligrams per kilogram per and kilogram is measured in ideal body weight.
When you look at the specific instructions for ideal body weight, it makes no logical sense on how they came up with this equation for this specific drug. It's really based on the patient's height and sex, whether they're male or female. In other words, in my inexperienced opinion and not having done several hundred of these, the dosing seems very antiquated.
It reminds me of back 15 years ago when we were using radioembolization and doing it based on BSA formulas and having arbitrary cutoffs for lung shunt fraction. That's what it brings me back to. The good thing is that the FOCUS trial used this dosing data and got their published results. In theory, if we can try to optimize the dosing over the next two to three years, maybe we can even get better results.
Can we optimize the dose based on the patient's tumor burden, based on liver volumes instead of body weight, and so on and really figure out how to drop the dose in those cases of neutropenia, as Altan mentioned. Is 2.5 sufficient or do we keep the same dose? Is it really dose dependent and so on?
All these variables, I think we can optimize in the next two to three years, especially as more centers come online and we try to collaborate and share data, that hopefully, the results will get even better than they are right now.
[Dr. Altan Ahmed]
Yes, definitely a big opportunity there Covey and Sid, as you mentioned, to start looking at tumor volumes and liver volumes and see if there is a better way to do this.
[Dr. Siddharth Padia]
To me, it makes no sense if you have 40% tumor burden versus 2% tumor burden, we're giving the same dose.
[Dr. Altan Ahmed]
Absolutely, yes.
[Dr. Siddharth Padia]
That doesn't really sit well with, I think, most of us who do chemo and radioembolization because that's not how we do those two procedures.
(7) Optimizing Treatment Cycles & Patient Response
[Dr. Venkatesh Krishnasamy]
Right, great point, and we'll see. I think only time will tell as the intervention evolves. What about cycles of treatment? The FOCUS trial was six cycles of treatment or up to six cycles of treatment. Not everybody got all the way to six. There's some patients that in Europe, Europe has had CHEMOSAT, which is what they call it for over 10 years now.
They've got up to, Altan, I don't know off the top of my head, eight to nine maybe cycles, something like that. Where do we envision that going in the US?
[Dr. Altan Ahmed]
This is one place where I feel like there is going to be improvement, especially with CHOPAN and some of the combinatorial therapy trials coming out soon. Is it necessary to go all the way to six treatments or can we get to a steady state where we have response and patients are stable?
They either have, hopefully a complete response, but that's not going to be the most common finding. They have a significant response. You do your combination therapies of PHP plus whatever else may be there. Then do you watch and wait for a little while or do you just keep going until you have progression?
I don't know ultimately what the answer to that is going to be, but Covey, I think, some of our discussions with our European colleagues has been that they've started to err on the side of fewer treatments and watching and waiting. Sid, what has your practice been like so far?
[Dr. Siddharth Padia]
It's funny because I think the three of us with some others had this email conversation several months ago about, when do you pull the trigger for the next treatment? I think we're all over the map and I don't know if any of us are right because I don't know if there's a right answer. We've been playing a more conservative approach to what you're saying.
I'm not trying to get a complete response on everyone and just going, you're going to get six treatments up front. I see this more of a marathon and not a sprint. This is not curative in intent, just like most therapies for stage four cancer. The goal is to get longevity while preserving their quality of life.
To me, the best thing that makes sense is to stretch these out a little bit, to try to get some objective response, but then maybe perhaps hold. We don't even necessarily go to four treatments if we're getting a response after two. Is that the right answer? Only time is going to tell. It does remind me of our evolution in experience in treating patients with neuroendocrine tumors, which I know that, for example, the Moffitt Group has a lot of experience with.
Where we would go-- when we were starting out over a decade ago, going very aggressive, trying to hit every little thing and finding out that you have no options two to three years down the road, or you because liver fibrosis and so on. Now what we do is a much more patient-paced, methodical treatment algorithm for these patients where we're only picking off enlarging tumors or big tumors and so on.
We're not seeing hepatic fibrosis or bad vasculature anymore. We're able to stretch these patients out for over five years, and sometimes now even approaching 10 years. I think we can try to do the same thing with HEPZATO as well.
[Dr. Venkatesh Krishnasamy]
That's a great point. This is a non-embolic, non-liver toxic therapy. We're walking the line a little bit because even in the FOCUS trial, there was a significant portion of patients that required at least two treatments to show response. At the same time, as you said, we're not going after a complete response.
Just loading the drug, loading intervention, and then having bone marrow toxicity down the line can be a problem as well. Spacing those treatments out, as Altan alluded to, we don't know the right answer and hopefully we'll figure it out over the next three to five years.
[Dr. Siddharth Padia]
We still don't know, is this better? Is radioembolization better for uveal melanoma? There was one analysis published out of Europe looking at a propensity score match retrospective of about 35 patients in each group, which suggested that percutaneous hepatic perfusion was superior.
Again, it's really one study. We're still trying to figure out our algorithm. I think one of the big advantages of this therapy of HEPZATO is that it is non-hepatotoxic. The rate of liver decompensation is extraordinarily low. In every single patient I've treated, we've measured their LFTs afterwards, not even their AST or ALT will budge, even the next day. It really does seem to be pretty benign on the normal hepatocytes.
[Dr. Altan Ahmed]
I think that's going to be a huge thing for the future. Sorry, Covey.
[Dr. Venkatesh Krishnasamy]
No, go ahead.
[Dr. Altan Ahmed]
I think the chronic liver toxicity is just not there. Ultimately, what this is going to mean is that we're not really burning bridges for the alternatives, whether it's Tebentafusp or whatever may come down the line later. This is huge for the patients. If we can preserve the liver, get control of the disease, we're just extending their lifespan here.
[Dr. Siddharth Padia]
We're even starting to integrate this with radioembolization. Someone might get radioembolization, they may have a good response, they may progress in the future. Then can we switch to this or vice versa. It's nice to have this other tool that we can use for these patients that does not have overlapping adverse events.
It's not the same adverse event profile. In other words, you can figure out how to mix and match these therapies. Of course, from a data perspective, it's going to be very hard to tease this out. It allows us to just offer more therapies that are individualized and personalized for patients.
(8) Patient Post-Treatment Management & Adverse Effects
[Dr. Venkatesh Krishnasamy]
That's a great point. Do you treat the bulky disease with, a RADSEG type approach and then come back and treat the rest of the liver knowing that there's probably miliary disease elsewhere with PHP. It makes a lot of sense. We just don't know the answer to. I want to back up real quick. Sid, tell me, how are you managing these patients post? What are the other risks that you've seen or adverse effects that you've seen so far?
[Dr. Siddharth Padia]
Like everything, we took a very conservative approach in the beginning and then we've liberalized it a little bit with time. In the first two to three patients, we would always put them in the intensive care unit. We realized that was overkill. In our practice, we're using closure devices, just like we use clear devices for our other procedures.
We are now sending them to our standard PACU, we keep them overnight. In actually some cases, we've been sending them home the same day after four to six hours. Our post-op is really, they get a platelet transfusion at the end of the procedure. We do measure their CVC at the end of the procedure to make sure that they're not thrombocytopenic or have a low hemoglobin.
We transfuse if necessary. We're typically discharging them within 24 hours of the procedure, either the same day if they're done in the morning or we keep them overnight and send them home. I think the one thing that's different is we do a reasonably close follow-up with labs within the first week.
The biggest thing you want to watch out for is a drop in your white count, which then needs to be at least addressed. Again, there's no huge consensus, but in terms of how to address it, one way is just observation and just follow it until it normalizes, or the other one is to give them a white cell stimulator, which is an injection.
Those are the two options. I work with our oncologist to figure out what is the best option. The oncologists that I work with, I would say, are a little bit different in their approach than I think most other oncologists. They are not big proponents of giving injections for white cell stimulators, so their preference has been to let that white count will always drop a little bit.
Their preference has been to let it just drift back up on its own. I think that is in contrast to most other centers, which are probably more aggressive in addressing it pharmacologically.
[Dr. Venkatesh Krishnasamy]
Altan, how about you?
[Dr. Altan Ahmed]
Yes, I think that's a good point. I don't know what the right answer is for this, but our practice is typically, we'll admit them overnight to the ICU. We are not currently using closure devices here, but all our patients do get a white cell stimulator within 48 to 72 hours of the procedure, usually before discharge, so a little bit different than that.
Close follow-up for laboratory findings, particularly the CBC, the nadir on the white count drop is typically within the 10 to 14 day time range. Within the next week after the procedure and then weekly thereafter for about four to five weeks until, the patient has stabilized and is rebounding.
[Dr. Venkatesh Krishnasamy]
That's a great point. Bone marrow recovery can take a little bit of time, in your experience, generally in that two to three week time frame for both of you?
[Dr. Siddharth Padia]
Interestingly, in our experience, after procedure number one, it's been quick. After, let's say, procedure number three or four for that same patient, it's taken longer for them to recover. Altan, have you guys seen the same pattern?
[Dr. Altan Ahmed]
Yes, similar here. I guess, the additive exposure to melphalan is it delays the recovery a little bit.
[Dr. Siddharth Padia]
Ironically, the overall tolerability of the procedure, surprisingly, even with all these accesses, cardiovascular effects, anesthesia, and so on, the patients return to pretty much normal after about three days. Most of my patients are returning to work, even if it's a physical labor in terms of their jobs, within a few days, other than, soreness at the access sites.
It does seem like the physical recovery is faster with each successive procedure. Pepsodo number four, they seem to tolerate really well compared to the first one, which is in direct contrast with the bone marrow recovery.
[Dr. Altan Ahmed]
Very similar to what we've been seeing as well.
[Dr. Venkatesh Krishnasamy]
Going back to the quality of life issue, so really not a lot of quality of life issues. I know we have some quality of life data. I think the Southampton group and then, correct me if I'm wrong, gentlemen, more recently the Leiden group as well, maybe, but showing, return to function fairly fast, as you both said.
[Dr. Siddharth Padia]
Yes, I would say that the biggest effect is the anesthesia. They're undergoing general anesthesia for a few hours, so you're going to have the effects of anesthesia. The other side effect is we do see some patients, not all, with nausea for, I don't know, maybe up to a week. We're pretty aggressive with our anti-nausea regimen.
We really ramp that up. Scopolamine patches, Odansetron, sometimes Compazine PRN. We're very aggressive in that, and that has helped in terms of battling nausea. I'll be honest, I don't even know if the nausea is from the procedure or from the anesthesia.
[Dr. Venkatesh Krishnasamy]
I wonder sometimes are some of these effects related to excessive melphalane exposure? Let me lead you down this path. You have a patient's getting a first-time treatment, has severe bone marrow suppression. Do you think that's an individual patient issue or maybe the balloon leaked a little bit more melphalane systemically than we thought? Something like that, Altan? I don't know. What's been your experience?
[Dr. Altan Ahmed]
Oftentimes, I think it's a patient-specific thing, and we start to look for answers. Anything specific anatomically in this patient? Is there anything we can identify in retrospect that we could change? Oftentimes, it's usually a patient-specific thing. Sid, what has your experience been?
[Dr. Siddharth Padia]
Have you ever found anything, Altan? We've looked at all our patients and I don't know, I can't-- To me, it seems like dumb luck that it happens.
[Dr. Altan Ahmed]
Yes, pretty much. When you go back and look at it, there was a publication a while back looking at the leak and doing some specialized imaging on the DSA to actually quantify the degree of leak at the cranial balloon. Ultimately, I don't know that any of those patients, their time course or the way they tolerate the procedure would have changed at all.
It's not something that you would change on the fly, I don't think, in terms of dosing, at least.
(9) Gaps in Current Intervention & Future Research
[Dr. Venkatesh Krishnasamy]
Great points. I think that's very helpful. Obviously, unanswered questions. That brings me to the next question. What are the other-- we've talked about some of the gaps in the current iteration of the intervention. What are the additional gaps that are out there that we need to address with future research? Tell me, guys.
[Dr. Siddharth Padia]
I think one of them is to stratify patients. Right now, for better or worse, let's say from a tumor perspective, we're taking all comers. In other words, the requirement from a tumor perspective is to have multifocal bilobar disease. Now, does that mean you have 1% tumor burden, or does that mean you have 40% tumor burden?
If we can start better stratifying those patients, uvea melanoma looks different on every patient. Sometimes you have these T1 tiny little bright lesions. Sometimes they enhance like HCC with arterial enhancement and washout. Does it respond better in those HCC-type looking lesions, or does it respond better in these bright T1-type lesions?
Because I'm starting to-- and these are all anecdotes, but I'm starting to see different patterns of response based on what their baseline MRI looked like. I think that if we can start to tease this out, to figure out who it's working in and who it's not, we can start then saying we should be aggressive in terms of approaching patients or offering this to patients where we think the success rates are going to be higher and so on.
[Dr. Altan Ahmed]
That's a great point, Sid. There is obviously a spectrum within the uveal melanoma disease process itself. There's some who are more prone to developing metastases in the first place with certain genetic markers and whatnot. Does that also influence how they respond to these treatments?
That's going to be very interesting to see in the future, for sure. I think another part of it is, optimizing dosing we had mentioned and touched on a little prior. Then seeing is there anything we can change in terms of filtration in the future? Is there going to be a better generation of filtration? Can we extract more of this melphalane to minimize the systemic side effects?
Then looking at other histologies as well, I think that's the next natural step here as well.
[Dr. Venkatesh Krishnasamy]
We've gone down this path for other interventions. Sid, you alluded to it earlier within the early 90 days, we treat with BSA, then we moved to MERD, and now we've moved to partition, and we have threshold dosing for a lot of our tumors. I envision that in this space as well. Again, better patient selection, better filtration, and then hopefully stratifying, which patients are going to have optimal outcomes versus less optimal outcomes.
Maybe we still offer the intervention in that intermediate category of, some benefit but not, great benefit, especially if there's nothing else to offer. Helpful to know, helpful to educate the patient as to what to expect, right?
[Dr. Siddharth Padia]
Absolutely.
[Dr. Venkatesh Krishnasamy]
We've talked a little bit about already where this fits into the current algorithm of uvea melanoma. I personally have moved away from radioembolization, especially for miliary disease, not just for melanoma, for everything, unless it's a very hypervascular lesion and I have a great TNR. How do you both feel about Y90 for miliary disease in this disease type?
[Dr. Siddharth Padia]
It's a great question. If you look at the Y-- I actually think the Y90 data for uvea melanoma is quite good. The best paper comes out of Karen Gonzalves out of Thomas Jefferson, where she did a Phase 2 prospective study. Her response rates were very good. They're actually in the same league as HEPZATO in around 30% objective response rates based on resist.
It's unfortunate that, it's not FDA indicated or FDA approved for this specific indication, which does handcuff us a little bit. The miliary disease, when you-- if you have a patient with a bunch of little dots throughout the liver, if you actually measure their overall tumor burden, it's still relatively low. It's going to be 10% or maybe even less.
What happens is when you're doing a radioembolization, you have to treat the whole liver. You're going to get-- almost impossible to quantify it, but you're going to get a good amount of normal hepatocyte radiation deposition. Those are the patients I try to shy away from, not because it's not going to have any tumor response, but those are the patients that you will see higher incidence of liver-related adverse events in contrast to a single 6 centimeter hypervascular tumor, which is the exact opposite.
Those patients with 20, 30, 40 tiny little dots scattered throughout the liver, I think HEPZATO is a great option because it is non-hepatotoxic.
[Dr. Altan Ahmed]
It's been the same in our practice as well. Moving away from Y90 for the miliary-type pattern of disease. HEPZATO has not had those chronic liver effects that we mentioned earlier. Then local localized disease, definitely Y90, if you can get there through a segmentectomy, that's fantastic.
[Dr. Siddharth Padia]
Yes, and I've seen a lot of patients with-- I hear this argument that if you see one 5 centimeter tumor from buvio-melanoma in the liver, that means it's all over the liver. I don't believe that at all. I've had lots of patients where I've treated that one 5 centimeter tumor and they've had prolonged response for even on the order of years.
I'm happy to show examples to other people that that's not necessarily a case that if there's smoke, there's fire. I don't think that's necessarily true all the time. You have someone with one or two or even three tumors that are solid, that are well circumscribed, that are focal, that you can target selectively, radioembolization to me is my go-to therapy in those cases.
[Dr. Venkatesh Krishnasamy]
Yes, that's a great point. The other thing I'll add to that, and, we know this from other disease types as well, that preoperative MR or CT can sometimes be a little bit misleading. You get a catheter into place, you do a cone beam during the intervention, and you may see other spots light up and that may change your treatment algorithm a little bit. To your point, I totally agree with you. If you just have isolated bulking disease, then I think you both mentioned it, radiation segmentectomy type approach is totally relevant.
[Dr. Siddharth Padia]
Altan, what pre-op imaging are you getting prior to your cases?
[Dr. Altan Ahmed]
Typically, MRs.
[Dr. Siddharth Padia]
With a specific type of contrast or just anything?
[Dr. Altan Ahmed]
Anything. It's usually not any of those. We just use the standard.
[Dr. Siddharth Padia]
We've been using Eovist MRs for these patients and we found that we're picking up a lot more tumor than, let's say, a CT, which is night and day.
[Dr. Venkatesh Krishnasamy]
On the delay phase?
[Dr. Siddharth Padia]
Yes. If you look at that 18 to 19 to 20 minute Eovist MR, you end up seeing a lot more tumor than you really thought there was going to be.
[Dr. Venkatesh Krishnasamy]
That's a great point. Then maybe a little more apples to apples to the artiography and co-mem CT.
[Dr. Siddharth Padia]
I think that even these limits of 50% tumor burden and so on, when you deal with PHP or even any other local regional therapy, especially melanoma, if 50% on a CT with IV contrast and you do that MR with Eovist, it'll be 99%. It'll be completely replaced with tumor. I think that's where people are saying, oh, you're getting adverse events if you have 60% tumor burden. In reality, you don't have 60% tumor burden. In reality, you have 99% tumor burden and the patient's dying of liver failure from tumor infiltration.
(10) New Applications for PHP Therapy
[Dr. Venkatesh Krishnasamy]
Great point. All right. I want to end on one last question and I fully recognize that this is reaching into the future a little bit, but where else can this therapy be applied? What other tumor types-- you both know this question was going to come. What other tumor types can we utilize here?
Where are the other gaps in our IR armamentarium that we really don't have something to offer that PHP in its current iteration or a future iteration can fill those gaps? Sid, why don't you start?
[Dr. Siddharth Padia]
Good question. I think right now it's going to be still isolated to liver, just the way that the kit is designed. In terms of other organs, let's just assume we're talking about liver. Then we want to talk about--
[Dr. Venkatesh Krishnasamy]
Sorry, I meant medical disease and liver.
[Dr. Siddharth Padia]
Yes. Unmet need. The unmet need I think is the biggest one is colorectal cancer. That's probably number one on the list. It's probably-- none of them are going to be easy to study. That's one of the challenges because you have so many different lines of systemic therapy. You're going to have to study this in a trial. You can't just-- Altan and I can't just start doing this in colorectal cancer. That's not going to work that way.
We would have to do this on a trial. How do you design that trial, let's say in colorectal cancer, when they have good first or even second line options, they have now genetic subtypes and so on. It's not as easy to design these trials in the other malignancies. Breast cancer is another one, but that one's even harder because you have now 15 different lines of systemic therapy. Where do you put this?
If you even get oncologists, forget about us, you get five medical oncologists in breast cancer, where would you insert this? Even in a trial, you'll get five different answers.
[Dr. Altan Ahmed]
A very loaded question for sure, but I think I'd agree with Sid. I think colorectal is the next natural histology to look at. It's not going to be easy because where do you insert this therapy? First and second line are great. Second or third line I think is an opportunity there. There is a pretty sharp drop off in systemic therapies from second to third line, the efficacy of those therapies.
That's where we would get some referrals for Y90 and whatnot. Maybe we can insert PHP there and see how these patients do. Honestly, I think the biggest deal is going to be that we're not seeing that chronic liver disease. A lot of these chemotherapies are very hard on the liver. You guys can think back to all the referrals you get for breast, colorectal, whatever it may be.
These patients, their livers take a pretty big hit from these chemotherapies. There is an opportunity there. Where it's going to fit in exactly is still a question mark, and I don't see it happening outside of a trial setting. It's just going to be very challenging to generate high-quality data without that.
[Dr. Siddharth Padia]
There are some case series and very small series out of Europe. I think the challenge is they're challenged by numbers as well. They had seven or eight patients. It's very hard to make conclusions from seven, eight patients.
[Dr. Altan Ahmed]
One really promising thing, really, I'll just add on to that a little bit, is, the IHP data from the surgical procedure has shown pretty significant response rates for colorectal already in the 50-60% range. There is a precedent to use this methodology there as well.
[Dr. Venkatesh Krishnasamy]
I think to both of your points, there are also two separate patient populations with colorectal or with any metastatic disease. You have the oligometastatic population where you can pick off individual lesions either with RADSEG or thermal ablation or both or whatever. Then you have the more widespread disease across both lobes where something like this may be a little more applicable.
You're right. I think trial setting and hopefully, we can rely on some of that data that has been brought up and we'll figure it out as we go forward. Altan, you also have some specific experience with cutaneous melanoma, correct?
[Dr. Altan Ahmed]
Right. Our center, like I said, has been doing this for over a decade. Sarcomas, cutaneous melanomas are areas where we've explored this in the past. The response rates, have been pretty reasonable. I think the challenge is there are-- cutaneous melanoma is one of these things. There's a huge disparity between the progress that's been made in cutaneous melanoma versus uveal melanoma.
Immunotherapy has revolutionized the treatment for cutaneous melanoma. Dicarbazine was FDA approved over three or four decades ago. That same milestone wasn't reached until we had to Tebentafusp, and that was in 2022. It's just been a blank slate for uveal melanoma. I think there's a little bit of a challenge in having this fit in other places. This would be more of a salvage. I see it working in that setting.
[Dr. Venkatesh Krishnasamy]
That's super helpful as well. All right, gentlemen, I think our time is up. Any final thoughts? Any final words?
[Dr. Siddharth Padia]
No, that's it. I think it's great that we have another promising therapy. Keep in mind it's new. We have, I would say, more questions than answers right now, which is a little bit daunting, but also a little bit exciting as well.
[Dr. Altan Ahmed]
Absolutely. Very exciting time for sure. I think collaborating across disciplines, medical oncology, surgical oncology is a real opportunity here to make some good differences for a lot of patients here.
[Dr. Venkatesh Krishnasamy]
Absolutely. Great points. Thank you to our listeners. Thank you to you both. Fantastic information. Great dialogue. I appreciate both of you being on here today, this early morning on a Sunday, and we'll catch up soon.
Podcast Contributors
Cite This Podcast
BackTable, LLC (Producer). (2025, March 4). Ep. 522 – Advancements in Treatment of Metastatic Ocular Melanoma [Audio podcast]. Retrieved from https://www.backtable.com
Disclaimer: The Materials available on BackTable.com are for informational and educational purposes only and are not a substitute for the professional judgment of a healthcare professional in diagnosing and treating patients. The opinions expressed by participants of the BackTable Podcast belong solely to the participants, and do not necessarily reflect the views of BackTable.
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