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Sam Chang: Hello everyone. My name is Sam Chang. I'm a urologist in Nashville, Tennessee. And we are joined today with Dr. Amy Luckenbaugh. I've known Dr. Luckenbaugh for many years now, actually, as she completed her residency at Michigan, and completed her fellowship, actually at Vanderbilt with us, and is currently an assistant professor in the Department of Urology at Vanderbilt of Nashville, Tennessee as well. And she is going to discuss how she's helped to initiate a program of treatment of a novel or new agent, that's been approved for treatment of patients with low-grade upper tract urothelial carcinoma.

That agent is called JELMYTO^®. And she has led our efforts to treat actually upper tract with this agent, and actually initiated that, a program giving it via an antegrade administration. So doing that was not a small feat. And so first, I want to say thank you, Amy, for helping to bring that to Nashville and to Vanderbilt. And secondly, I think you have a presentation that kind of goes over that process as people are trying to think about initiating such a program. Kind of what you helped design and implement, and look forward to your presentation. So thanks for being with us.

Amy Luckenbaugh: Thank you so much for having me. So as Dr. Chang mentioned, I helped to establish this treatment algorithm for antegrade administration here at Vanderbilt. Honestly, with the help of people from outside who had also helped to do this in other locations. And that was a huge thing is talking to people who have done it before.

And so, in brief, low grade, upper tract urothelial carcinoma can be a little bit of a pain to treat, especially endoscopically. It can be hard to ablate completely with the laser fibers of visualization. And so JELMYTO^® came around when they did a Phase III open label trial. And this medication is a reverse thermal hydrogel, that you instill either retrograde, through a ureteral access catheter, or antegrade, through a percutaneous nephrostomy tube. And it fills the renal pelvis and conforms to the pelvis. And after four to six hours it is slowly excreted. So it allows that dwell time that a pure liquid may not.

And so, this study administered this weekly for six weeks, and then also went on to allow maintenance for those who responded once a month for up to 11 months. And they had really good outcomes, with a complete response of 58%. And this is mainly for tumors that are between five and 15 millimeters. And of note, you can ablate a tumor to get it to that small, and actually, if it's 15 millimeters it can still be given, even to those who have visible disease, which is a little different than the bladder cancer literature.

And so, we do it antegrade here, for a couple reasons. Some, it's logistics. There also is newer recent data that perhaps people who have it administered antegrade have lower rates of ureteral obstruction or stenosis. So as you prepare to administer this antegrade, make sure that your OR template when you perform ureteroscopy has a couple things. Things like the size and location of tumors. Because this may impact where you would want to place your PCN, if you're going to be administering this antegrade.

Also, measure the renal pelvis volume. Usually this is done three times, just with contrast. And then you take the average of those three values, and that is essentially how you know to dose the JELMYTO^®. And the alternative to that is when radiology places the PCN, they can measure the volume with that method. However, oftentimes it's a little harder for them to do it three times. So I would just encourage you, when you do ureteroscopy, to have that built into your template if you are thinking about JELMYTO^®.

Sam Chang: So Amy, in your operative note now, you make clear kind of all those components, is that correct? The location and size of the tumors, as well as in the volume. And the volume, you say, you just use contrast and just measure how much you instill with that syringe to emphasize, okay.

Amy Luckenbaugh: Yes. And it's usually on average like eight to 10 ccs approximately. It's usually on average. It's never more than 15 ccs, so we don't usually administer more than that.

Sam Chang: Got it. Okay, good, thanks.

Amy Luckenbaugh: Yeah. And so then we have interventional radiology place a percutaneous nephrostomy tube. And we actually have the patients cap that as soon as interventional radiology is okay with that. So they're not walking around with a bag, or anything like that. A week later, they come in and an antegrade nephrostogram is performed by radiology to confirm that the PCN is in good position, mainly still in place. And then the patient comes directly to our clinic, and we flush the PCN, aspirate to confirm that urine is there. We check a urinalysis to make sure they don't have an infection. So similar to administering medication for bladder cancer. And then we instill the JELMYTO^®. And so that is, again, a reverse thermal gel. The goal is to instill it over 20 to 60 seconds. You don't want to take too long. And after you administer that, you do a 2 cc saline flush, and that just clears the PCN tubing, and gets all the JELMYTO^® into the kidney.

And then we cap the tube. And I tell people to leave it capped, unless as the week progresses on, that they have pain, in which case they could uncap it. And I think that's another benefit. If they are having signs of obstruction or discomfort, they can uncap the tube, with no impact on the treatment.

And so, this is the device that is used to administer the JELMYTO^®. It's very self-explanatory. And each treatment is done once a week for six weeks. So each time the patient comes in, we confirm tube placement by flushing and aspirating. We only do that first antegrade nephrostogram. We don't do one every week, we just do one at the initial first visit.

Sam Chang: That is an advantage, compared to the retrograde administration then, I guess. Because you have to always know where your uretal catheter is, at least by fluoro or have an idea. So once you do it once, and you know it's in good location, and it drains and it aspirates, then you're comfortable in terms of being able to seal. So okay, great.

Amy Luckenbaugh: Yes. Yes. Then we're comfortable. We instill it by the same method every week, and we cap that tube, and we do that for six weekly treatments. The week after their sixth treatment, we have them come back, and this is the second antegrade. And this may be an unnecessary step, but we decided, as an institution, to do this, to make sure that before we pull the nephrostomy tube, that they don't have a new obstruction. And so, if there's no obstruction, then we remove the PCN, and we do a surveillance ureteroscopy somewhere between eight to 12 weeks after completion of their JELMYTO^®.

And that is the protocol here at Vanderbilt, I currently, and we don't really do the maintenance JELMYTO^®. Simply because having people have a tube in for a year to get once a month maintenance I think is a lot. And some of the studies have kind of shown that maybe that maintenance is unnecessary, especially if they had a good response upfront.

Sam Chang: So Amy, that was a great presentation. I just want to now ask some basically logistical questions as people start to chain this. I learned a lot in terms of the placement, the confirmation, the importance prior to actually starting the treatments, of actually gathering the data, which we don't necessarily always have thought about beforehand. I haven't thought about getting the volume measurements, and being very, very careful in terms of size and location of the tumors. Tell me what you did in terms of logistics with the interventional radiology team. Do they know these patients ahead of time? Or are they identified as JELMYTO^® patients? Or tell me about setting up your throughput system with interventional radiology.

Amy Luckenbaugh: Yeah, absolutely. We actually developed this protocol with the help of one of the interventional radiologists. He's actually the one who thought that we should do an antegrade prior to removing the PCN at the end of treatment, before burning that bridge, in case they did have obstruction. And so communicating with them was helpful. We do send it to a specific person and tell them, "Hey, this is for JELMYTO^®. We may need renal pelvis volumes, and here's why we're doing this antegrade, and please send them up afterwards." We also, if we want the tube placed in a specific location, based on the tumor, then we tell them that information as well. And so, I think that's all important to communicate with them, in order to make sure that patient flow is as good as possible, and perhaps that treatment as good as possible. There isn't evidence that one location is better than the other or anything like that, but I think it is something logistically that makes sense.

Sam Chang: And for the tube placement, you want to avoid placement then in a high volume tumor area, is my assumption, is that right?

Since you're getting the full pelvis anyway, you want to avoid that. So that location and then working with the same intervention radiologist clearly is helpful. How long do you leave the nephrostomy tube then after that sixth treatment? When do you get that follow up antegrade nephrostogram?

Amy Luckenbaugh: Basically anytime within a week, like a week after, as usually when I started again, I do see them one week after we've completed it and do that antegrade nephrostogram. It could stay longer if there for some reason they have travel issues or things like that. But it's usually not a shorter duration just in case the particle, the gel is dissolving and going to cause symptoms we leave it in for that week after.

Sam Chang: Great. And so have you had any issues, in terms of a complaint? Sounds like a small nephrostomy tube and it's capped off, and so really, no issues in terms of patient discomfort, I would bet.

Amy Luckenbaugh: Not really, no. The thing that alarms patients most is that their urine turns blue, and their stool can turn blue too. So that's something to tell them. That's honestly the thing that has bothered or alarmed people the most. Rarely they have some pain within like 24 hours or so of the administration. And to me, I think that's when the gel is passing through the ureter, and it can mimic kidney stone pain, and that's when having the option to uncap can be beneficial for them. And they don't really complain about the nephrostomy tube being present, because they don't have to have a bag.

Sam Chang: So in terms of next steps, as you started treatment, treated patients and that type of thing, do you see any upcoming kind of modification for the algorithm? Have you considered one time stick, and then that first stick give a treatment? Or I think we're emphasizing safety first, but what do you think may streamline it even further?

Amy Luckenbaugh: I think potentially, now that we know from large larger studies that the rate of obstruction is lower with people who are receiving it this way, we potentially could actually remove the tubes right at the end after that last dose, rather than create a second visit. We haven't quite gotten there yet, because we do want to be careful, safety first, but I think that's one possibility. I also think they don't necessarily have to wait a week per se, to get the first dosage of treatment. And so, if someone travels from far away, and radiology is willing to do two placement antegrade, and then the next day do treatment, I think that would be a viable option as well.

Sam Chang: Well, Amy, thank you so much for spending some time with us, and giving some practical advice, in terms of those individuals. I mean, the little tidbits regarding the blue urine, the placement, the tube, the measurements, understanding kind of safety first, with the role of the nephrostogram, and being able then to have the patients uncap if there's any questions, concerns, I think are really important, and kind of critical kind of take home nitty-gritty type messages.

So thank you again for starting the program at Vanderbilt, and we look forward to continuing to treat these patients in this unique way. And we'll continue, I will continue, to follow your meteoric rise in the world of academic urology. So thanks for everything.

Amy Luckenbaugh: Thank you so much. Thanks for having me.