Natalie Callander, MD, of the University of Wisconsin joins HealthTree Podcast to discuss kidney disease in multiple myeloma.

Dr. Callander shares how many patients are faced with the dual challenge, what causes kidney issues at diagnosis and after relapse, how kidney disease is managed, drugs that can help or hurt the kidneys and how patients can use and get off of dialysis. Listen or read this important show to better learn how to manage this very common co-condition. 

Thanks to our episode sponsor, Takeda Oncology

Jenny: Welcome to today’s episode of the HealthTree Podcast for Multiple Myeloma, a show that connects patients with myeloma researchers. I’m your host, Jenny Ahlstrom. We’d like to thank our episode sponsor, Takeda Oncology, for their support of this program.

Before we get started on the show today, I'd like to make you aware of our HealthTree Myeloma Coach Program. Our Coach Program includes over 200 experienced myeloma patients and caregivers, volunteers, who can help you navigate your multiple myeloma with one-on-one support. You can use one or multiple coaches, and you can select a coach that looks right for you. Coaches have experience on specific issues like finance or other topics or specific myeloma therapies like CAR T or stem cell transplant. They can work with you by phone, on the computer or in person if they live in your area. You may have noticed also that we are moving over from myelomacrowd.org to healthtree.org/myeloma, and we hope you can use that new link for all of our support programs. If you'd like to find a Coach, you can go to that URL and then look in the menu, under Apps and Programs.

Now onto our show. We know that a large percentage of multiple myeloma patients develop kidney issues, and this show is dedicated to understand the management of kidney concerns better with the help of Dr. Natalie Callander from the University of Wisconsin. Dr. Callander, welcome to the program.

Dr. Callander: Thanks very much. My pleasure to be here.

Jenny: So nice to have you. Let me just give you an introduction for you before we get started. Dr. Callander serves as Director of the Myeloma Clinical Program and Interim Director of the Bone Marrow Transplant Program at the University of Wisconsin. She's also professor of Medicine, Vice Chair of the NCCN Myeloma Committee, and attending physician at the William S. Milton VA Medical Center. She's also a DOT Leader of the Myeloma Disease-Oriented Team and Chair of the Bone Marrow Transplant Clinical Trials Network Intergroup Committee. She graduated magna cum laude from Yale University and has been named as one of the Best Doctors in America for over a decade. She's also received a Chuck Koval Award for Excellence in Myeloma from the Leukemia Lymphoma Society. She's listed as one of Madison Magazine's Top Doctors in Hematology, and has won a Patient Experience Physician Champion Award from the University of Wisconsin for multiple years.

Dr. Callander leads many clinical trials that have led to approvals for myeloma drugs, so we're very grateful for your efforts in growing the myeloma arsenal for patients. Impressively, on your CV, I saw that you served as a Major in the US Air Force for almost a decade.

Dr. Callander: I did.

Jenny: While you were doing your residency. I'm just so impressed with that. Thank you for your service. It's amazing.

Dr. Callander: Yes. Well, I am happy to be here to talk and answer any questions as this can be a little bit complicated. Please stop me, Jenny, if what I'm saying doesn't seem to make a lot of sense.

Jenny: I think we'll start with the basics. Basically, can you explain, what is kidney disease?

Dr. Callander: Well, the kidneys are a paired set of organs that are basically mid back. They're behind the abdomen, if you want to think of it that way. Of course, their job is actually complex. They are there to regulate water, also to regulate sodium and potassium. They have a major impact on blood pressure. They also supply an important hormone called erythropoietin that is essential for red blood cell production. They are really very, very critical organs.

Jenny: What happens when the kidneys get damaged? How would you define chronic kidney disease?

Dr. Callander: Yes. There's a very strict definition of what that is. Now, kidney function is often measured by what's called glomerular filtration rate, and that comes from a part of the kidney called the glomerulus which is like a squiggly little bit of membranes where exchange of wastes and fluid take place. The formal definition of chronic kidney disease is if your function is reduced roughly by a third for more than three months. That translates, if you're looking at your labs, into a reduction in glomerular filtration rate, typically under about 60 milliliters or CCs per minute, which is a lab that you can usually find, or maybe it's calculated in your chart.

Jenny: Is there a difference in myeloma? Is it considered chronic kidney disease, or is it just kidney disease?

Dr. Callander: There are many ways the kidney can be affected when you have myeloma. Roughly speaking, about 20% of people, when they first get diagnosed with myeloma, have some sort of kidney disease. You can split it up into a number of different problems. One problem or one group of problems that people can get with their kidneys related to myeloma is directly related to the abnormal proteins myeloma cells are making, the immunoglobulins. Probably, the most common problem is something called cast nephropathy. That is a term where the light chains, either kappa or lambda, are so high in the bloodstream that as they are passing through the blood that is being filtered in the kidney to remove the waste products and water, those light chains start to accumulate and literally clog up these tubules that are there to help remove water. You can get clogging. There's also something else called a monoclonal immuno deposition disease, and this is where the monoclonal protein that the myeloma cells are making actually sticks to parts of what's called the glomerulus and causes problems that way. That's a little bit more rare.

Of course, some people with myeloma also have amyloid that ends up in the kidneys, and that ends up causing a lot of potential destruction of some of these very, very tiny and important components in the kidney. There are problems that can occur that are not related to immunoglobulins, and that includes things like having high calcium can be harmful to the kidney. If you get very dehydrated, that can be harmful to your kidney, if you get a bad infection. Every once in a while, we see people who have myeloma that's actually growing into the kidney, but that's relatively rare. Finally, there are some other immune-related disorders that can be accompanied by the myeloma, things that lead to what's called glomerulonephritis, where there's actually inflammation of this very important component of the kidney. That can cause things like high blood pressure, and occasionally, some blood in the urine. There's a number of different ways that the kidney can be affected.

Jenny: Just generally speaking, a lot of people who have maybe, they already had chronic kidney disease from things like diabetes and high blood pressure. Do you want to just talk to that before we jump into all the myeloma-specific cases?

Dr. Callander: Yes. Well, I think it's very important if, for example, if you are newly diagnosed with myeloma, and you know, based on perhaps you've had annual visits in the past with a primary care physician or provider, and you know that your kidney function was never abnormal, that's a very important piece of history to share with whomever is taking care of you. Sometimes a person comes in the door with kidney dysfunction, and we will not be sure if part of that dysfunction is related to high blood pressure or diabetes. Some of the different types of problems that I just listed there that can happen in myeloma, more and more, we do recommend people have a biopsy of the kidney because sometimes it's not clear exactly what's going on. Disorders like diabetes and high blood pressure can actually cause some scarring of the kidney that may not be reversible, so I think it's very important to try to figure out what might be a component directly related to myeloma that may be treatable and may be fixable versus something that was there at baseline. So, often, a kidney biopsy can be very helpful.

Jenny: That will be part of your myeloma diagnosis workup, I guess, that's what you're saying.

Dr. Callander: Yes. Well, excuse me, I mean, sometimes I've seen people in a situation where they come in with their creatinine, now creatinine is one of the measures of kidney function that we use. There are really two that people look at. Creatinine, basically, the higher the number is above one, usually that corresponds with a decline in kidney function. There's also something called blood urea nitrogen or BUN, or some people pronounce it bun, that is looking at the filtering capability of the kidneys. If a person walks in the door and their creatinine and BUN are elevated, part of what is your job as a myeloma provider is to try to figure out how much of that is perhaps new and old. Sometimes it's very clear that a person probably has just that cast nephropathy, or just an overwhelming amount of light chains is causing the problem. I do think sometimes we're surprised, and that's why I think a kidney biopsy can be very, very helpful.

Jenny: That's so interesting. I didn't know that was part of myeloma workup if you had kidney issues.

Dr. Callander: Well, I think you could really be surprised. Previously, a number of years ago, I think there was more reluctance on the part of a kidney specialist or a nephrologist to consider a biopsy. I think, over the years, more and more people have realized that this is actually a very helpful thing to do.

Jenny: What percent of patients do you see walk in as a newly diagnosed patient who has kidney issues or advanced renal disease?

Dr. Callander: As I mentioned, it's around 20%. Unfortunately, over the years that people are living with their myeloma, you can develop kidney problems later on. Sometimes the nature of the problems that you have with your myeloma changes as well, but the rough number’s about 20% have some kidney issue that needs to be addressed. There are a percentage of people who come at the time that their myeloma is diagnosed, who appear to need support with dialysis right off the bat.

Jenny: Okay, and what percentage is that? Do you know?

Dr. Callander: I would say it's about five. Often, they are people who may actually have some underlying kidney problems to begin with, or somebody who, for whatever reason, it took a relatively long period of time to make that diagnosis of their myeloma.

Jenny: So interesting. Are there any other symptoms that can indicate kidney disease beyond the lab values that you might notice?

Dr. Callander: Sometimes there are different symptoms in different situations. If a person has high calcium, sometimes that causes symptoms, like increased thirst, occasionally, people will have abdominal pain and constipation related to that. Those can be tip offs. There are some times where people come in, and I ask people this specifically because, often, people do report this. We ask, does your urine look foamy or bubbly? That can be a sign that you have very high levels of protein in urine, of those light chains. That's something that we ask. Sometimes people will say that they are having some changes in the color of their urine that it looks a little dark Coca-Cola. That sometimes can be associated with some specific kidney problems, but many, many times, people come in and actually feel okay. They don't really have a specific issue that that we would say, a-ha, this is related to your kidney problem. Now people who have very severe kidney failure, which is fortunately really a minority, sometimes, they come in and have gotten into a situation where they're nauseated or vomiting, or they're confused because of waste products that are building up in the system. Fortunately, very few people come in the door with that.

Jenny:  I think that might have been one of the reasons that I went in, well, not the nausea or confusion, but one of those others, just to get tested for myeloma. You talked about the labs and the BUN and creatinine counts. Are there different counts for the African American community? Because when I look at my lab, sometimes in my chart, it'll say there's a difference between the, is it eGFR value? I can't remember.

Dr. Callander: Yes, which stands for estimated glomerular filtration rate. For many years, what was done in labs was a calculation where patients who are African American will tend sometimes to have a little bit higher creatinine, and this was factored into an estimation of what the estimated glomerular filtration rate was. What was happening as a consequence is that, particularly if patients, and this is not related so much to myeloma, but if patients were African American and waiting on, say, a kidney transplant, they were being unfairly having an overestimate of how good their kidney function was. There was actually a taskforce set up in 2016 to try to address this problem.

There is an equation out there called the chronic kidney disease EPI or CKD-EPI, and this is based on looking at GFR based on sex, age and level of creatine. There is no factor of ethnicity, and that's considered a more accurate way to do it. There's an even more accurate way to measure GFR, if that's important, measuring something called cystatin C that can be done. That tends to be done more by nephrologists. We don't do that much in myeloma, but there really was a time when the calculations that were used were overestimating the GFR in patients who were black. I think that's changing more and more, which is appropriate.

Jenny: Okay. We talked about how kidney disease is affected by myeloma, you walked through that very well, and other factors that can contribute to it. Are certain myeloma patients more prone to kidney disease? Let's say you have light chain only myeloma, or you have IgG Kappa myeloma or IgA or genetic factors.

Dr. Callander: There has been some association with the type of monoclonal protein that is made and the development of kidney issues. As many of your listeners may know that the most common type of protein that a person makes with myeloma is IgG kappa, but a fair number of people will make an IgA monoclonal protein.

IgA has been associated with a somewhat higher risk of having kidney problems. Of the two types of light chains that a person can have, kappa and lambda, lambda has been associated with a higher risk of kidney dysfunction. It's really quite relative, Jenny. It doesn't mean, okay, if I have IgA lambda multiple myeloma, I am guaranteed to have kidney problems. It's not that exact. It's just more of a tendency. Certainly, people can come in the door with IgG kappa myeloma and have very severe kidney dysfunction. It's all relative, not absolute if I can say it that way.

One thing I would want to talk about, just in terms of other factors, and probably something that many people listening know, there are a number of medications that we actually try to get our patients, if they are having any sort of kidney issues, to stay away from, and those would be drugs like, what are called nonsteroidal anti-inflammatory drugs. Those would be things like ibuprofen or Motrin, or Aleve, which is naproxen. Those drugs can potentially cause some kidney dysfunction. There are some other blood pressure medicines that sometimes you have to be a little bit careful with, what are called ACE inhibitors. Those are drugs like Lisinopril or Enalapril, sometimes can have a chance of causing some kidney dysfunction. That's another thing that we try to do when a person comes in the door, and we're trying to look at their kidney function. Along with those two classes of drugs, sometimes people come in, and they're on big doses of a diuretic like a water pill, maybe hydrochlorothiazide to control their blood pressure, for example. Those are relatively easy things to do that can make a big difference to stop them and help improve somebody's kidney function.

Jenny: Yes, so instead of having to leave or those types of things, you typically recommend something like Tylenol.

Dr. Callander: Certainly, there are situations, all of this stuff is relative. There are times when nonsteroidal drugs turn out to be quite helpful for bone pain, but there are definitely people, particularly those who have an abnormal creatinine, who probably are better off staying away from drugs like that and thinking about some of the alternatives like Tylenol, for example.

Jenny: Some of that can be long-term use. Let's say you had a lot of pain for some other cause, or even myeloma you didn’t know was myeloma, and you're taking it all the time. What you're saying is, that NSAIDs can end up damaging the kidney more than you want it to.

Dr. Callander: Then there are prescription only nonsteroidal drugs that are used sometimes for arthritis. For example, there's a drug called Mobic, which is the trade name for a drug called meloxicam. Sometimes people, for example, if part of getting to a diagnosis of myeloma, somebody thought, for example, you were having bone pain from arthritis, they might have had you on that kind of drug for a while until they knew the diagnosis. That can certainly be quite a harsh drug on people's kidneys, and one that we would try to stay away from.

Jenny: Okay. Interesting. If you have a newly diagnosed patient walk in with some kidney issues or damage, how do you handle that?

Dr. Callander: What we try to do is, since, as I mentioned, the most common reason they're going to have kidney dysfunction is they're going to have these light chains that are clogging up the kidney. Most people think that the fastest you can bring down those light chain levels is the best. Historically, the drugs that we've used the most would be steroids. This is a situation where dexamethasone, even though it is not something that anybody wants to stay on, in big doses, long-term, can be very helpful if given for a couple of days. Bortezomib tends to be a very useful drug in this situation. You can also sometimes use daratumumab. Those last two drugs do not need to be adjusted for creatine, so we certainly like to use them.

Older approaches include using the drug, cyclophosphamide, which is an old, old drug that's been used for myeloma for many years. It has been a little bit controversial. There have been some centers that have done what they call plasmapheresis, which is a treatment to try to remove protein from the blood. It is not really clear that that is helpful. It's probably not as helpful as just making sure that a person's light chains are coming down from chemotherapy, but there are some places that still do that. There has been an attempt to try to make the plasmapheresis more efficient at removing those light chains, but those processes usually only remove a minority of the light chains. You still need to have some sort of effective chemotherapy going on.

Jenny: Treating the myeloma right upfront is your most critical issue.

Dr. Callander: It's really critical. What we always try to do, particularly if somebody is coming in, right off the bat, needing dialysis, is that's really a goal to see if we can get them off. We don't all the time, but you can very often get a person in a better situation by doing some aggressive chemotherapy. One of the things that I certainly like to do is check their light chains relatively frequently. We are hoping to see at least a 50% reduction in a situation like this, in a couple of weeks, just so that we know that we're on the right track and giving the kidneys every possibility of recovery if they can do it.

Jenny: That's a good question. Can kidneys recover after that type of thing?

Dr. Callander: They can. One of the things that's been gratifying about autologous stem cell transplants is we have absolutely seen people who have been on dialysis up until they have their stem cell transplant and then following the transplant, improve and are able to get off dialysis. I would love to tell you that it's the majority of people, but it is something that can happen. Kidneys do have the capacity to recover. We definitely continue to try to make sure, if a person has really significant kidney dysfunction, that we are doing everything that we can to put their myeloma in remission so that it would give the kidneys the maximum opportunity to recover.

Jenny: You mentioned stem cell transplant. It sounds like it makes things better. There's nothing that would preclude a kidney-damaged patient from getting a transplant. Correct?

Dr. Callander: Well, this is not true of every center, but most places are pretty comfortable doing transplants in people who are on dialysis. We do that basically because we believe that a transplant is a good way to control somebody's myeloma. Now, you have to have some experience doing this because it takes some scheduling. We're talking primarily about people on hemodialysis. We tend to use somewhat lower doses of the drug, melphalan, the one that's used for transplants in general, and we have to time the dialysis around the chemotherapy.

It is widely accepted that you can do a transplant even if you're on dialysis. Like I said, we know that a portion of those patients may recover. The other thing that can happen is there are times when we've had patients who eventually go onto a kidney transplant. Something that, of course, would be done only in a select group of people, but it is a possibility for a person whose kidney function doesn't recover, even though they're now in remission.

Jenny: That's so interesting. I have some friends who are dealing with that right now and emailed in some questions. We'll wait for that at the end, but we will cover that.

Dr. Callander: Okay.

Jenny: How about drugs that are harder on the kidney that are for myeloma care?

Dr. Callander: Usually, the drugs that are top of everybody's list that you have to be a little careful with are the immunomodulatory drugs, IMiD drugs, and that would be drugs like lenalidomide and pomalidomide. Lenalidomide, for sure, is cleared through the kidneys. It is a drug that we will use in people even on dialysis, but you have to use typically very small doses. As many of you know, the starting or top dose of lenalidomide can be 25 milligrams a day. In people on dialysis, we often do five milligrams, maybe one dose after dialysis, or even two and a half milligrams after dialysis, just very, very petite doses.

Pomalidomide is labeled as not requiring renal adjustment or dose adjustments downward. I would say, in my experience, that that is also a drug that we like to diminish in terms of doses at four milligrams, which is, again, the top dose is something that I think most people with kidney dysfunction actually don't tolerate very well, so we'll usually start at one or two milligrams

Carfilzomib is also a drug that is not really cleared. This gets a little bit controversial, depending on who you talk to. Carfilzomib has been implicated in some reports as actually causing renal failure, but I think that is a rare situation. It is a drug that has a track record of being given to people on dialysis. If somebody is having some heart-related issues like heart failure and are on dialysis, it can be a very, very tricky drug to use. That would be one that we would be pretty careful about giving. Some of the newer drugs probably don't need renal adjustment. For example, belantamab looks like you can probably give that with a low GFR. Selinexor, I think there's a little bit less of a track record for that. Almost every drug that we use, if you are very careful in the dosing, you can use it. It really takes just, I think, a lot of caution, I would say. Of course, as I mentioned, steroids are something that often can be given pretty easily in people who have renal impairment or on dialysis, as long as it's not causing a lot of fluid retention.

Jenny: Interesting. What about the newer immunotherapies like CAR T and bispecifics and things like that, what do you say about that?

Dr. Callander: There is more and more data that for CAR T transplants, that people with kidney dysfunction can go ahead and have a CAR T. The lymphodepleting chemotherapy tends to contain a drug called fludarabine, and fludarabine absolutely has to be reduced, and in some cases, omitted, depending on how much kidney dysfunction a person has. That's one consideration, but I don't think anybody believes that the actual process of giving somebody a CAR T is going to cause kidney problems. Unless, of course, there was a complication, like a bad infection. I think there's less knowledge right now with the bispecifics. Those particular patients were largely excluded from the trials if they had a GFR under 30 or 45. In the lower ranges, they seemed to be okay with it. I would imagine that some of the other drugs, I mentioned daratumumab really doesn't seem to have any renal toxicity. Isatuximab, we'd also put in that category, elotuzumab also.

Jenny: Monoclonal antibodies, you’re saying, just fine.

Dr. Callander: They seem to be fine. Yes.

Jenny:  I want to jump to a question later, but maybe we can talk about it now. You talked about clinical trials in CAR T that patients may have not been able to join those. Are there a lot of trials that exclude kidney patients for that particular reason?

Dr. Callander: There absolutely are. There are two cut points that are used often. In some clinical trials, if a person has a calculated GFR, glomerular filtration rate under 60, they are excluded. There are other trials that let that number be a little bit lower, under 30, or excuse me, as low as 30. There are very few trials that will either take a person who is on dialysis, or having a GFR that's below 30. Often, that's because some trials are looking for toxicity signals, and they're very nervous about having somebody who already has some kidney dysfunction on it. If the trial was something perhaps sponsored by a drug company, again, same thing, they're very interested in avoiding toxicity. They see that as an exclusion, but it makes it very hard. If you are a person who would like to go on a trial, but your kidney function isn't the best, it can be quite difficult to find one.

Jenny: Okay. Clinical trials, I understand the concept of wanting to get everything tested in a certain way and having a consistent patient base and all that, but sometimes it gets challenging for patients who are trying to try this clinical trial. They have something knocking them out.

Dr. Callander: Every once in a while, there are some trials that are specifically designed, but they've been tough. Years ago, they ran a trial looking at trying to figure out the right dose of lenalidomide or Revlimid within people on dialysis or with kidney failure. They actually had a hard time getting enough patients to be on the study because it can be a unique population. Sometimes, particularly early on, if people are coming in, and they're having very bad kidney dysfunction, they're also having other problems that are just making it hard for them to go on trials. Maybe their counts are very low, or there are other factors there. It is something that it's been, historically and actually, in reality, very hard to find trials for people who don't have a kidney function at least better than that 30 CCs per minute calculation.

Jenny: You talked earlier in the show about kidney disease that's diagnosed at the time of diagnosis where you tried to knock it down. You also said that kidney disease can be developed over time, over the course of certain myeloma therapy. Can you explain how that works and what patients look for and how it's treated?

Dr. Callander: One of the best things that's happening in kidney treatments is that many, many people are living longer and longer and longer, which is great. One of the things that I think we've learned now over time is that when a person starts to have their myeloma relapse, it doesn't necessarily have to be the same way it did before. In particular, sometimes people who had an M protein, very large monoclonal protein, IgG or IgA, at the time they were diagnosed, when they relapse, sometimes they're myeloma cells then choose to only make light chains. Occasionally, we'll see, because perhaps, maybe all that's being followed is, say, a serum protein electrophoresis and maybe not light chains, a person will end up relapsing, and now have kidney problems that are related more to the fact that they've got very high levels of light chains that they didn't have before. Everybody hates collecting a 24-hour urine test. Sometimes it can be very helpful to have that information, particularly at a time that a person's myeloma might be getting worse.

The other thing that happens is, sometimes it becomes very apparent later on that a person is actually developing some amyloid too. That might be a situation where a person starts losing very large amounts of protein in their urine. That can be something where you can see a drop in a person's albumin in the serum, which is a normal protein, and in amyloidosis, it can slip into the urine very quickly. That can happen later on, where it wasn't apparent at the time of diagnosis. Those are a couple of instances that we can see.

Jenny: For people who don't know what amyloidosis is, do you want to just describe what that is for a minute?

Dr. Callander: Sure. There's a whole spectrum of different disorders that involve plasma cells. By far, the most common one is multiple myeloma that tends to have things like anemia and bone problems related to it. There are more rare disorders, one of which is amyloidosis. Amyloidosis, the difference really with myeloma is there is abnormal protein being made by plasma cells, but what happens to that protein is quite different. There's a technical name for this, it becomes folded into what are called beta-pleated sheets. The basic concept here is that protein gets deposited in different organs, and that's what causes the problem. It's not that you have so many plasma cells that they're overwhelming the bone marrow, as you can see in myeloma, it's really the stuff that's getting deposited in organs that causes problems.

People will come in, again, with kidney dysfunction, but they also can sometimes get this amyloid deposited in the heart, and that can cause a very specific type of heart failure where the squeeze is okay, but the heart becomes very sickened. Sometimes people with this disorder can have nerve problems. They can have numbness and tingling. The amyloid can sometimes be deposited in very odd places, lymph nodes, occasionally it's seen in the tongue. Again, it's not so much that people walk in with bad anemia, like they often can with myeloma, but it's more where this protein is getting deposited. Now, it's treated, often, very similar to myeloma. A lot of the same drugs we use for myeloma, we’ll use in amyloid, but there are some very specific things that you have to watch for people who have amyloid as their primary problem, particularly if it's involving the heart.

Jenny: If you catch it early, you can reverse some of the conditions.

Dr. Callander: Absolutely. It's one thing we've learned over time. There was an era where it was thought, okay, the amyloid, particularly if it was in the heart, is just going to sit there and never get better. I would love to tell you it's in every patient, but it's not. In a substantial number of people, if we start treating them, and we control the production of that amyloid protein, that gradually improves in some patients. One of the things that people are excited about is that there may be some drugs on the horizon that could help reverse some of those deposits. I think people are very excited about that.

Jenny: Oh, that is wonderful. Okay, that's good news. Nice to hear. Okay, can we talk about kidney transplant for a little bit?

Dr. Callander: Yes.

Jenny: What's, what's the process to get on the list for a kidney transplant, and what's the criteria?

Dr. Callander: I think every institution that does kidney transplants, probably has a little bit of a different take on this. Certainly, I think what's happened over the last 15 years that's made this come up more often is several things. Number one is that our ability to get a person's myeloma into a complete remission is a lot better than it used to be. That's usually a criteria that kidney transplant centers will want you to achieve. They'll want you to say, okay, is your patient in a complete remission? Secondly, what they're looking for is, how healthy is the person in general. If somebody has had kidney dysfunction, bad enough to need dialysis, but they're also having heart problems, and they're also having lung problems; those patients are typically not going to be accepted for transplant.

It’s really, the kidneys are the isolated medical problem, their myeloma is now in remission, and some centers will have a cut off for how long they want that remission to last. In other words, some centers will say, well, we want it to be a minimum of two years or something like that. Now, this changes a little bit, at least in our center, the pool of related donors, that is living related donors, meaning somebody in your family or even a friend, or living, unrelated donor who comes forward and says, yes, I would be willing to donate a kidney. I think that pool is a lot bigger than it used to be. That has also opened up the opportunity. We've had, over the years, I wouldn't say it's tons, but we certainly have had people go through kidney transplants.

One of the things that gets a little bit difficult is particularly if a person has kidney failure, but they're still able to urinate, sometimes it's very hard to tell for sure that they're in remission. Occasionally we have had people who have gone through a kidney transplant, now that urine, that protein that they were losing is staying in their blood system. Now we can tell that they aren't in remission. We have had the experience as well of having to treat people who've been through a kidney transplant, treat them again for myeloma, but again, as our drugs have gotten better, that's become more possible. We have several patients who have had a kidney transplant, had their myeloma come back some years later, now they're back on some treatment for their myeloma, but the transplanted kidney is doing fine.

Jenny: Okay. Now when you say you have to be in complete remission, by what criteria is that? You're not talking about MRD negativity or anything like that.

Dr. Callander: Usually, it's been things like a complete remission, meaning you can't find a monoclonal protein in the blood. At least, for example, our program would ask that you have a bone marrow biopsy that also does not show any evidence of myeloma, and some places will ask for a PET scan. Like I said, there aren't hard and fast criteria that are being published nationally at this point, and there's still relatively small numbers of patients who are going through this. Like I said, I think there definitely are people out there who have gone through a transplant and done so successfully. One of the things that you do have to be prepared for is there may be a situation where you will have to treat somebody's myeloma again, and then you have to take into account, how do you protect that transplanted kidney? Because typically, those patients are going to be on immunosuppressive drugs to protect the kidneys, so it can be a little bit of a delicate balance.

Jenny: The only transplant process I understand is really stem cell transplant and allo transplant, when you're getting GVHD or things like that. In that scenario, do you have issues like that in the kidney world when you're doing kidney transplants while they’re on immunosuppressants?

Dr. Callander: Yes. For organ transplant, what you are worried about is typically the recipient can have immune cells that attack the new kidney. Those kidneys in general aren't coming in with a lot of abnormal cells from the donor, but the recipient can decide, hey, this is not my original kidney. This is something that I need to reject. They can, in turn, send immune cells that can get into the kidney and really harm it so that after a kidney transplant, people are given usually a cocktail, that's the term they will call it, of immunosuppressive drugs, usually an oral drug like tacrolimus, but often antibody drugs that are basically designed to knock down T-cell function. They're often given some steroids.

Sometimes, what we have noted is that those immunosuppressive drugs that they're on to help protect the kidney can actually have probably some degree of effect against the myeloma itself. I wouldn't say it's completely transferable that you'd say, oh, that's perfect treatment for myeloma, but there probably is some potential benefit towards myeloma. One of the things that they will do in a renal transplant versus what we do, say, after a donor transplant for a blood disorder is they will stay on those immunosuppressive drugs, often forever. There have been some moves to try to cut down on maybe not making it a lifetime commitment, but that is much more the practice than it is for, say, a donor bone marrow transplant where we do try to get people off immunosuppressive drugs.

Jenny: Now, that'd be interesting to study that in addition to, potentially, immunosuppressive drugs in myeloma, like if you've got a double hit or something like that.

Dr. Callander: One area of research, which is really fascinating is that there has been some discussion about using some of our drugs or our approaches like CAR T. There are people out there who would like to get an organ transplant but have very high production of antibodies against other people's tissue types, and that can be a very difficult situation. There's been some interest in using myeloma type drugs to actually treat people before a transplant to bring down those levels as a beneficial effect of some of these anti-myeloma drugs or a CAR T, for example.

Jenny: Wow, that's so fascinating. How do you know that in advance? Is there a donor type thing that you do?

Dr. Callander: Yes, they screen people. For a person who's been considered for a kidney transplant, what they would like to do is they screen you for what are called anti-HLA antibodies or human leukocyte antigen antibodies. Meaning, are you likely to react against other tissue types? If you have a very high level of these antibodies, it is very likely that you're going to have a kidney rejection problem. There are various maneuvers they can try to do to get those antibody levels down, but it's a big problem in organ transplantation, not just for kidneys, for other organs as well.

Jenny: Yes it makes sense. I'm sure that's a long process and probably not an easy process. Is there an average time to get on a waiting list to get a new kidney?

Dr. Callander: Well, one of the things that makes that time built in is that kidney dysfunction as opposed to, say, heart dysfunction or liver dysfunction is something that people can be on dialysis for a period of time. There is that kind of bias to say, well, of course, you can be waiting here, but then there is also some degree of size. If, for example, a child is needing a kidney, sometimes it can be hard to get a donor for that. I'm talking about a very tiny child. The average wait time right now is still about three to five years. I think that's why that's been the move to try to find people that are related to you or people who are friends of yours who might be willing to donate a kidney. If you've got a person like that, if you've got a living person who is willing to come forward, the wait times are much, much shorter. Of course, not everybody has that situation.

Jenny: Yes, that seems tough to time, like the length of your remission around your transplant too. That's a tricky challenge.

Dr. Callander: Yes and I would say, looking at the patients that I've had with myeloma who have undergone kidney transplant, there's a little bit of luck involved in it too. There's also, something I didn't mention is they would like to have compatible blood types if they can do it as well. That is one reason why they will certainly ask you, if you have somebody who could possibly donate a kidney for you. It's always faster. As many of your listeners know, there are two kidneys. By and large, they do test to make sure there are two, if you want to be a donor. Usually, that single kidney, once they remove one for the donation, takes over the work of the two kidneys and ends up just fine.

Jenny: That's great. I've had certain patients say that only certain centers will perform transplant on them due to the complexity of their myeloma. If they went to a regular transplant kidney center, they said, oh, sorry, you have these myeloma issues or whatever, you're going to have to go to X facility. Do you hear that a lot? How do you coordinate that kind of care?

Dr. Callander: We're fortunate here at the University of Wisconsin, we actually have a very large renal transplant program, one of the largest in the country. They're pretty experienced with various situations. As I mentioned, their biggest concern is, how well controlled is your myeloma or, for that matter, your amyloidosis. Those are things that they consider. They tend to work very hard to find donors for people. We've been working together for long enough that I think they're quite comfortable. They'll often say to me, okay, do you think this particular patient, is their myeloma in good enough shape? Could we consider a transplant? We’ll have a discussion about, no, maybe they should be on treatment longer; or yes, they're doing great, this would be a good time to consider it. I think that's one of the things that's been beneficial here is you just have a very good relationship with the transplant service, and they're very comfortable with us.

Jenny: I think this is a point I always stress too, just the idea of having a myeloma specialist on your team that can help coordinate this kind of care. Because I would imagine that sometimes even just the handoff from a nephrologist to a transplant center for kidney transplant is, I've heard, difficult. They don’t know where they are in the process or whatever.

Dr. Callander: I think the other thing is you could say, well, I'm going to go see a hematologist, not every hematologist may do a lot of myeloma. The same thing goes with kidney doctors, some kidney doctors, all they do is transplant at a large medical center. That's really their thing. They're not only just sending patients for transplant, but managing their care after they go through the transplant. Whereas, sometimes, if you're in a smaller or smaller, maybe more remote areas, that the nephrologist you may see is a general nephrologist and may not have those connections to a transplant center, or just may have assumed from maybe if they've trained some years ago, well, if you have a blood cancer like myeloma, of course, we would never consider a transplant for you. It's a small subset of people who are thinking about this, but it probably is the kind of situation where you would want to be seen at a real specialty center.

Jenny: We want to think about that all the time in myeloma as well, just whether we have a kidney issue or not, is finding a specialist like yourself to help with consultations and making treatment decisions and trying to navigate all the complexity of this type of thing. I have several more questions, but I also want to open it up for caller questions. In the MGUS or smoldering precursor condition stage, are there things that you suggest to MGUS or smoldering myeloma patients about kidney function? Here's what to watch out for. Here’s what to do differently or that type thing?

Dr. Callander: I think I have to credit the doctors at Mayo who took the lead on this, a number of years ago. There's an entity that is often abbreviated, monoclonal gammopathy of renal significance, or MGRS is the abbreviation. What that is, these are people who have kidney dysfunction that's significant. If you start checking your monoclonal protein levels, or a bone marrow biopsy, they don't actually make a definition of actual myeloma, but it's pretty clear they fall into that group. I think I mentioned at the very beginning, this monoclonal immuno deposition disease. That monoclonal protein, there may not be a lot of it, but for reasons that we don't understand, it is specifically targeting the kidney. These people, these patients don't tend to have anemia, they don't have bone disease, but they will have a creatinine elevation that's quite striking, and often have a lot of protein in the urine.

Even though you would say, well, they have fewer than 10% plasma cells, and they don't have any bone disease; these are people that, more and more, we're saying, that clone of plasma cells is clearly causing a problem. They should be treated and, in many cases, go through an autologous stem cell transplant, just like if you had a higher level of protein or higher bone marrow involvement. That's an area that's emerging. Again, I think, if you're at a larger center, many people, many nephrologists are very used to thinking about that now, but I think that's an area, if you have MGUS and your creatinine is very elevated, I'm talking about more than one. Let's say it's one and a half milligrams per deciliter or two, and you have MGUS. One thing you'd want to make sure is, hey, I don't have this, I'm not in that subset where that monoclonal protein is really what's causing my kidney dysfunction. Again, this is where a kidney biopsy really comes in because you can only really make that diagnosis of MGRS with a kidney biopsy.

Jenny: So interesting. So many things to think about. Again, in my opinion, if you're working with somebody who's just treating hematology generally, or you're in a general oncology community center, that might be tougher to pin down, just because of the time to see it.

Dr. Callander: This is, again, one of those situations where it is always, if you can, if you've got the information that you can access to be aware of where things have been. For example, if you know for sure that I never had kidney dysfunction ever in my lifetime, and now you tell me, I have MGUS. I have maybe one and a half grams of protein in my bloodstream, but my kidney dysfunction is I have a lot of kidney dysfunction. I would say, you need to make sure that those two aren't connected. Again, I actually really like it when people come in with notebooks and spreadsheets and things like that. It's usually quite helpful. People do an amazing job these days of tracking all of their labs, which, like I said, it's just excellent information.

Jenny: We provide the HealthTree Cure Hub tool for that, too, because you want to be able to track those main features. Sometimes, even if you have MyChart or something, I don't know, it's not the easiest tool to use. It's useful and good, but seeing it, over time, compared to all your other features, it's hard to do.

Dr. Callander: Yeah, because I think MyChart, I found a lot of patients, since we have Epic at our institution, who are quite frustrated with it. They just feel like, well, I can't see enough months in a row, or I can't see enough years. Sometimes not everything gets posted, so using tools like what HealthTree provides is great.

Jenny: Okay, my last question, how can myeloma patients protect themselves against kidney disease once they have it and while they have myeloma?

Dr. Callander: Well, I think some of this is really common sense. We try to get people to make sure that they're well hydrated, particularly in the summer. Or if you're living in a hot part of the country, we usually tell people we want them to drink somewhere between two to three quarts a day. Absolutely, we like people to avoid getting contrasts. For example, if you are getting a CT scan or a PET CT, we really want to be careful about contrast. That can be hard on the kidneys.

We already mentioned things like Aleve and Motrin and Advil. You want to be very careful with that if you know already you have some kidney disease. Let's see, other medicines out there, like I said, if you get started on an ACE inhibitor or diuretic, you just want to make sure that somebody's watching your creatinine. People sometimes ask, is there anything specific you can eat to make your kidney function better? I don't know that we really know anything.

There are some nephrologists who feel that too much protein is hard on the kidneys. Sometimes they'll try to limit protein below something like 60 grams, which really isn't that much protein in a day. That, I don't usually tell people that they need to get. A lot of times I'm more worried that people just make sure that they're eating enough. That sometimes can be an issue. I think keeping your myeloma well controlled is another big factor in all of this too.

Jenny: Wonderful. Okay, well, I want to leave some time for caller questions. If you have a question for Dr. Callander, you can call 347-637-2631, and press 1 on your keypad. Go ahead with your question.

Caller: Hi. Yes, I just was wondering if there are any treatments or medicines that can be tried as a last effort to try to recover any kidneys that were damaged as a result from multiple myeloma?

Jenny: Maybe prior to transplant.

Dr. Callander: That is a very interesting question. I think sometimes there are. One of the things that you'd want to figure out is, just what we were addressing earlier, are you really in remission or not? If you're in remission, it can be pretty tough to just say, well, I'm going to treat your myeloma more, and that's going to make the difference. Sometimes, it really takes a little bit of effort to figure out if that's the case. Recently, some of the patients that we've had who had some kidney dysfunction, turned out to carry in their myeloma cells, something called a translocation of 11;14, or it's a rearrangement of what's called cyclin D1. People who have that change in their myeloma cells tend to be fairly susceptible or fairly responsive to a drug called the venetoclax. Venetoclax is used widely in lymphoma and chronic lymphocytic leukemia and in people who have that change. I've seen some people who've had some pretty significant kidney dysfunction, who received venetoclax often with daratumumab, and it had some really excellent responses to that.

I think that's what I would try to figure out first is whether in remission, and then, are there other agents that haven't been used? If you are in remission, and your kidney function isn't recovering, I don't know that that's going to be helpful. Like I said, sometimes we have had patients go through a repeat kidney biopsy to say what's there. If they end up having just scar tissue, I think that tells you, all right, there's really nothing that you can fix. Versus, if somebody has, say, an active cast nephropathy, or they have this immunoglobulin deposition, you can say, aha, I'm going to really try to treat somebody to make that better, to make that go away.

Caller: Okay. Awesome. Thank you.

Jenny: Okay, thanks. There are no kidney-specific drugs, right? You're talking about treating the myeloma and hoping the kidney can recover, but there's nothing you can really do to treat the kidney?

Dr. Callander: No, but this is, like I said, kidney biopsies, which used to be considered, well, that's so invasive. I think this is, again, something that can help a person. If you say, I really want to find out whether there's still some kidney that's still able to recover, that can be a very helpful way to figure that out.

Jenny: Okay, great. Okay, another caller, go ahead with your question.

Caller: Hi, Dr. Callander. My question is, is there a procedure or treatment for clearing out the tubes in the kidneys that were damaged by the abnormal myeloma protein?

Dr. Callander: Except for treating the myeloma and hoping that they recover, no. There's no Roto-Rooter or anything like that that you can do to flush them out. As I mentioned, sometimes at the beginning, people will try, along with just treating the myeloma, a plasmapheresis procedure that's done in some places, but we don't, unfortunately, have a great way to just flush out the kidneys, except for drinking things.

Caller: Okay. Thank you.

Dr. Callander: Okay.

Jenny: Okay, great. Well, Dr. Callander, I know we're at time. I just want to thank you so much for doing the show with us. This is an important issue for patients. It's something we hear a lot about in different venues on social media and in some of the calls that we get and things like that. I just want to thank you so much for sharing your expertise.

Dr. Callander: My pleasure.

Jenny: Thank you for all you do for patients. Thank you for helping to get these drugs approved and just treat patients so incredibly well. Thank you so much for joining today.

Dr. Callander: Okay. Take care, everybody. Thank you for your questions.

Jenny: Appreciate it. Thank you so much for listening to this episode of The HealthTree Podcast for Multiple Myeloma. We invite you to join us next time to learn more about what's happening in myeloma research and what it means for you.