Neha Pathak, MD, FACP, DipABLM: Welcome to the WebMD Health Discovered podcast. I'm Dr Neha Pathak, WebMD's Chief Physician Editor for Health and Lifestyle Medicine. Today, we're going to discuss multiple myeloma, an often misunderstood cancer that affects your immune system's plasma cells.

We'll explore how lifestyle factors like exercise and plant-based fiber rich nutrition may offer early-stage benefits and why a supportive whole person approach is crucial. For anyone facing this or any other chronic condition, we'll highlight some clear takeaways on prevention, diagnosis, emerging therapies, as well as the value of treating the whole patient from physical symptoms like pain to emotional and mental well-being. Treating multiple myeloma is more than just treating that single diagnosis. about multiple myeloma, have a loved one navigating treatment or simply want to learn more about cutting edge cancer therapies.

This conversation will leave you with a greater understanding of what's possible and what's on the horizon in the fight against myeloma. Join us as we speak to an oncologist and nurse practitioner specializing in the treatment of multiple myeloma. , let me introduce my first guest, Dr Jens Hillengass.

Dr Hillengass is professor of oncology and chief of the myeloma and amyloidosis service and vice chair of research of the department of medicine at Roswell Park Cancer Institute in Buffalo, New York. He's a leading expert in the diagnosis and treatment of hematologic diseases with a focus on myeloma and its precursor conditions.

Welcome to the WebMD Health Discovered podcast, Dr Hillengass..

Jens Hillengass, MD, PhD: Thank you so much for having me.

Pathak: So, I'm really excited to dig into our conversation around multiple myeloma, but before we do, I'd love to ask about your own experience. own health discovery, whether it's in your research or your work with patients, that was really an aha for you and shifted the paradigm in how you're thinking about the work that you're doing.

Hillengass: That's a great question and a very loaded question. Of course. I started treating and diagnosing and doing research in myeloma over 20 years ago now back in Germany where I'm from. And I had a great mentor who was the myeloma attending at the time in, in the center in, in Heidelberg, Germany.

And what I learned was that the hallmark, and we will talk about it in more detail later on, but the hallmark of myeloma is the bone disease. And that is something that kind of followed me over the whole course of my career because patients oftentimes are diagnosed late and the bone disease is such threatening or for the patients, it's not only physically demanding, but also emotionally.

So what I do in my research, I want to diagnose it early. I want to treat it well. And I want to help my patients to live a life that is as good as possible. And another area which is connected to this is that myeloma currently, and I always stress this with my patients, myeloma today is considered not curable, but I think we are getting close to curing the disease.

But until we can really say we cure myeloma, I want to have my patients who have the best quality of life they can have. And bone disease is a very important part of that. So that's kind of what my, my association with myeloma and also my driving force is in part, why I went into this field.

Pathak: So then let's take a step back and really define what multiple myeloma is.

Hillengass: Yeah. that's something that I will give you kind of the talk that I give to my patients. Usually multiple myeloma is a cancer of the immune system or cells of the immune system. Those cells are called plasma cells. And in the healthy body, we all have plasma cells. Those cells are fighting infection by producing antibodies.

And what they do is when there's an infection coming into the body, a germ or whatever plasma cells that are residing in our bone marrow, where we have our blood forming organ that renews our blood, those plasma cells come out and fight the infection by producing antibodies.

They proliferate, become more and produce more and more antibodies until the infection is over. And then they go back into the bone marrow and wait until another, another infection comes in, and then they fight that infection. This is obviously a continuous process, but if something goes wrong, those cells kind of become malignant, they, they continue to proliferate, even though there's no need from infection perspective, there's no trigger anymore.

They just autonomously proliferate and produce more of this protein. And that's one of the things that we oftentimes see first that we find this protein in patients, that is wrong. We call it monoclonal protein because it's kind of one set of cells that continues to produce, the protein, which is not targeting against anything anymore.

Right. And that's what's causing the myeloma. And I think we will talk about symptoms later, but this is in part also what causes the symptoms of myeloma, this overproduction of proteins and this proliferation of this malignant plasma cells.

Pathak: And can you talk a little bit about risk factors for developing multiple myeloma?

Hillengass: Yeah. That's also a very important topic. And oftentimes patients ask me, what have I done wrong? And I can with good conscience say you have done nothing wrong. We know it’s not like smoking causes lung cancer. We don't have that in myeloma. myeloma is fairly rare. It's a second most common hematological cancer, the blood cancer, but it is still common enough so that we have some epidemiological, uh, data, we know that it's more common in people who have been exposed to toxins.

For example, painters, farmers, there are large epidemiological studies, for example in Scandinavia, where they have large data sets. That is something we do know that radiation exposure seems to have an effect. But it's also not clear. Not every patient who has been exposed to radiation gets myeloma.

Not every patient who has myeloma has been exposed to radiation, but it seems to be a contributing factor. But patients oftentimes ask if family members have an effect. We know there's a slight increase in family members, in first degree family members, but it's also not a real familial or hereditary disease.

So those are factors that we know about. I have a few patients who are veterans, who have been exposed. So again, toxins seem to have an effect. There's some data and it's actually accepted at the VA as a service-related disease. But those are the things that we know about. And what really triggers a patient to become a myeloma patient or to develop myeloma is not really clear.

There seem to be genomic effects. And they also seem to be immune effects because it's an immune cancer. It also suppresses the rest of the immune system and the surveillance that the immune system has on our body. Sometimes or on cells that are kind of developing to become cancerous. That seems to be suppressed in myeloma patients as well.

Pathak: And when are people most commonly diagnosed with multiple myeloma and is there a gender differences?

Hillengass: Yeah, that's also a great question. The median age statistically is 69 years. But I do have patients in their 20s and they do have patients in their 80s and 90s. So it is a wide range, but the peak is around 70 and that is the one thing that makes it I think for providers more important to look in this group of patients, but it makes it challenging for younger patients.

They oftentimes not diagnosed because no one thinks of multiple myeloma, right? And from a gender perspective, it's more common in male than in female, like a lot of other cancers. We don't think, there is a clear kind of reason for that, it's just statistically more common. What I find very interesting, and we don't have a good answer why that is the case.

We know it's more common in African Americans. It's actually double the incidence compared to Caucasians and Caucasians have it more common than Asians and Pacific Islanders and Native Americans. We don't have good answer, or I don't have good answers why that is the case, but we know African Americans have the highest risk and also interestingly enough, again, not clear why, can develop it earlier in their lives.

So my African American patients are usually younger, almost 10 years younger, in the median compared to the Caucasians that do have a better prognosis on the long run, which might be associated with a younger age. But yeah, we don't really know why that is the case.

Pathak: And I'd love to just reflect back on your earlier point around toxic exposure. So you mentioned something, with regard to farm exposures. Could you share a little bit more about that?

Hillengass: It's not clear. They think herbicide like in these studies, but they kind of went deeper analysis. What they think that herbicides might have an effect. But that's also the case for other hematological cancers like leukemias can also be, for example, related to benzene exposure. I just recently had a young patient who has been a truck driver and was exposed to fumes.

I looked into the literature just recently and it's very difficult to say there was something in petrol workers and the petrol industry, but nothing really clear cut that you can say, okay, if you're exposed to this, you will most likely develop myeloma. That's not the case.

Pathak: So can you share then some of the common symptoms that one might have? And you said that sometimes there's like a long runway before finally that diagnosis. Can you talk a little bit about that journey?

Hillengass: So there are four main symptoms. The major symptoms of myeloma are the so-called CRAB criteria. C R A B. C for hypercalcemia, high calcium in the blood, which is not very common, but it can happen, especially in later stages when there's really a long time until a disease is diagnosed.

The R stands for renal damage. These proteins that I mentioned earlier, these wrong antibodies, the monoclonal protein that is produced by these malignant cells can clot up the kidneys, which then can cause kidney failure. Anemia is a low blood count, which is because these cells, as I mentioned, they grow in the bone marrow, and they replace the normal bone marrow and then the bone marrow cannot produce enough blood and one symptom can be an anemia where the red cells are low.

And the fourth is the bone disease, which is one of the most common ones why patients are diagnosed when, patients develop. Lytic lesions in their bones, meaning the myeloma cells over activate otherwise healthy bone eating cells that we all have to rebuild our bone to if we have a fracture or if we, have to adjust our skeleton, we have bone eating and bone building cells.

And multiple myeloma cells can over activate this bone eating cells called osteoclasts and that can cause like in imaging. They look like punched out holes in the bones that can cause pain and then it can also cause fractures within again causes pain. And this is. most of the time, located in the back.

So in the spine and therefore back pain is a typical symptoms by patients are being diagnosed with myeloma, which makes it of course, very challenging because a lot of people, especially in advanced age have back pain and most of them don't have multiple myeloma. So that's a bit challenging. A lot of times patients go to their doctor with back pain and the doctor treats their back pain as they should, right?

But then the myeloma is missed because back pain is so common, and myeloma is so rare.

Pathak: And it's also interesting because, you know, when you think about kidney dysfunction and anemia, if you're coming into my primary care clinic and I'm checking your sort of routine labs or I get a CBC and a basic panel where I'm looking at your kidney function, is there a period in which you might see some of these abnormalities before you see a lot of symptoms that you've developed?

Hillengass: Yeah, absolutely. As you mentioned, oftentimes those are actually a lot of patients are diagnosed early because they are worked up for back pain. other symptoms or even other diseases. And then all of a sudden, a doctor orders the, because something is wrong, for example, in the kidney, the doctor orders a protein panel, and then these monoclonal proteins are being diagnosed.

And there are early stages. We know that every patient who develops myeloma has precursor stages before that. It has been done a very nice study where they went back in, in veterans who developed myeloma. They went back in and collected samples that they had stored at the VA. They went back and found that every patient who develops myeloma had a precursor before.

Oftentimes it's not diagnosed because they either don't have any symptoms or they have very unspecific symptoms like tiredness, fatigue, which is a very common symptom as well. But we know that there's a precursor stage and sometimes, and there's a continuum and we know that sometimes the kidney function starts to deteriorate, or the hemoglobin starts to drop.

And then with the bones is usually the pain starts when the disease is actually there, right? Back pain can have a lot of other reasons. Once the disease actually happens, then the fractures happen. And then sometimes even the lytic lesions themselves are painful for the patient.

Pathak: So can you dig a little bit deeper and tell us a little bit more about these stages from precursor to the stages of multiple myeloma? 

Hillengass: So the earliest stage that we know of is called monoclonal gammopathy of undetermined significance. I know that's a mouthful. We call it MGUS, M G U S. And that is defined as no symptoms caused by these cells. We don't even call it a cancer. It's a pre cancer precursor to cancer and patients have less than 10 percent of these malignant cells in the bone marrow.

If a bone marrow biopsy is done, they don't have symptoms, they don't have anemia caused by this. They don't have renal damage, don't have bone damage. And that's a very early stage. And generally, what we say patients with an MGUS who have been by accident being diagnosed with an MGUS have a risk of about one percent per year to develop myeloma.

Then there's this in between gray zone that we call smoldering multiple myeloma, where the patients already have more than 10 percent of these cells in the bone marrow, but still no symptoms. And they, those patients have roughly about 10 percent risk per year to develop multiple myeloma. And then the last stage is the multiple myeloma.

There's one stage beyond that it's called plasma cell leukemia, which is a very aggressive. It's still the same biology, but usually these myeloma cells are very dependent on the bone marrow. They the nurturing cells around them. and if they overcome this need, then they are found in the peripheral blood.

But that's very, very rare. But that's a so called plasma cell leukemia, which is kind of the most advanced stage of this disease.

Pathak: So before we jump into treatment, given the fact that I am primary care and prevention is just such an important part of everything that I do, I'm really intrigued and would love if you could talk a little bit more about that. So that risk, that escalating risk per year. Is there anything that people can do to mitigate that risk over time?

Hillengass: Yeah, that's a question that I get a lot from my patients, especially in the early stages. We actually have done a study where we gave out questionnaires about depression, anxiety, and we found that the early stages, the patients already had the same level of depression and anxiety as an active myeloma patient, because we tell them you have a precursor, you might develop cancer, even if it's a low percentage, it's still the word cancer in the room, right?

And those patients really struggle with that and ask, what can I do? There's unfortunately not much data. There is some data coming out now. There are active studies going on. One is looking into nutrition. and Dr Shah from the Memorial Sloan Kettering Cancer Center in New York does an amazing job in, changing diet of patients.

And what she has published and is working on is a plant-based diet, a fiber rich diet. The theory is that fibers, make the gut microbiome, the bacteria we have in our bowels, make them happy and they can proliferate, and they interact with our immune system, which then again has a stronger way to keep the disease under control, even in early stages.

This is very early data, so it's not really confirmed in larger numbers, but there's some theory behind that. And what we in our group is, working on is, to use exercise. We have early data to show that physical exercise improves the immune function. And what we know there's something called T cell exhaustion.

T cells are cells of our immune system that are very important in fighting cancer cells. And, over the course of the disease, those cells exhaust. And what we try to do is to make them fit. In the literal word sense, overcome their exhaustion and improve their fitness to keep the myeloma cells under control.

But that's at the moment more hypothetical. We have not been able to prove that yet. We have shown it in symptomatic patients. Now we want to show it in early stages as well. 

Pathak: What are some of the current treatment options that are available to patients?

Hillengass: I always when I tell my patient, okay, you need treatment and this is what we are going to do. I started treating myeloma, as I said, over 20 years ago and we had then one new drug. So we had two drugs to treat myeloma. We had a few others, but we are not using them anymore because they're not actually very effective.

So we had a chemo drug that kills cells that are dividing fast. It's called melphalan. We still use it as something called high dose chemotherapy. But that's such an aggressive treatment that we need a so called stem cell transplant, where we basically do a backup of the bone marrow and then give strong chemotherapy and then give the stem cells back, which is so called autologous stem cell transplant.

Autologous means from the own body, from the patient. but nowadays we have numerous treatments. We have different approaches, how to treat the disease. One is so called proteasome. They stop the cells, the cancer cells from producing certain important life, important life like vital proteins, and they also keep them from getting rid of all the protein they're producing.

So they basically more or less suffocate from their protein. That's one class of drugs. We use a lot of drugs that are engaging the healthy immune system, which I mentioned is very important. So that gives the immune system back this ability to fight the cancer. They're called immunomodulatory drugs.

We use a lot of antibodies where the antibody attaches to the cancer cell and also engages the immune system to kill the cancer cells. That's another group of drugs. And what has been very recent is being even more specific in engaging the immune system by engaging the so called T cells. And what we do, we collect these T cells out of the patient and tweak them, give them the ability, to develop a surface protein that attaches to the cancer cells, to a protein on the cancer cells.

And those cells are called CAR T cells, chimeric antigen The cells, and that is kind of the newest and most exciting treatment that we have together with so called by specific antibodies, where we also engage the T cells to kill the cancer cells. There are other drugs also where we keep them from getting rid of tumor suppressor genes out of the nucleus.

So we have a wide variety of drugs that we can use. We barely use chemotherapy anymore. We almost always use these targeted and immunotherapies in myeloma nowadays. And we combine, mix and match, and then, we get very good responses.

Pathak: Is there something that you're doing to sort of, individualize or look at the profile of your individual patient to help you do that mixing and matching.

Hillengass: Yeah. So what we have done for a while is there are certain genetic changes we can find in the cancer cells. We do a so-called FISH, where we look at certain chromosomal changes, and we know that some of them are more aggressive or. signaling a more aggressive disease. We call them high risk markers.

And we, for a while, we have treated high risk patients more aggressively. Nowadays, we know that even standard risk, I mean, it's always unfortunately that high risk patients don't respond as well as standard risk patients, whatever we do with them. So, we do individualize it to a certain degree based on the performance status of a patient. 

So if a patient is very frail, we would get less treatment. and also, if a patient is really elderly and we know, okay, we can keep them in remission for a very long time with the very mild treatment. We might not overburden them with a very toxic treatment, but we know now that even like a combination of four different drugs can be very effective in elderly and frail patients.

And oftentimes what we see is if a patient is very frail. They oftentimes are frail because of their disease. And once we get the disease under control, of course, not being too toxic, but then the patients actually get better and then they can tolerate better treatment. So there are a lot of factors that are coming into play and comorbidities.

For example, if there's a heart issue in play, or if patients have something called neuropathy tingling numbness in their fingers or toes, which is common in diabetic patients, then we would adjust our treatments because there are some side effects that are overlapping 

Pathak: I'm just really curious about what's exciting you the most about what you're seeing in the world of research, future directions that you are seeing that are up and coming that really animate you.

Hillengass: So one is definitely those CAR T cells and those bi specific antibodies, because usually when we get a new drug approved for multiple myeloma, the response rates in very late lines where we use them in very late lines where we have no other options, then it's ethically okay to offer a patient something that has not been approved yet.

So for example, in a clinical trial, and oftentimes the response rates then are around 30 percent with a bi specific and this is antibodies. In this case it was 60 to 70 percent and with the CAR T cells it was 80 percent, which is really outstanding. And now we use those drugs earlier as we do, we try them in late lines and then we use them earlier and we have just fantastic outcomes, patients achieving such a deeper mission that even with very modern diagnostic technology, we cannot even diagnose the disease anymore.

It's kind of almost gone. We still know that the disease can come back because our tests are not just not sensitive enough, but patients can be in remission for many, many years. And that is very exciting to me. And then also this lifestyle interventions that we already addressed earlier. I really think we can make our treatment better.

We can make the lives of our patients better. And I'm very excited in combining very active treatments with improving the quality of life, but maybe even the efficacy of these treatments by improving it, the host, the patient themselves.

Pathak: Thank you so, so much for spending so much time, sharing all of this knowledge with us. I'd love to yield our last few minutes together and just see if you have any final, thoughts on someone who's listening today, what they should know, action items that they might be able to take to improve their lives. If they or someone they love are managing multiple myeloma.

Hillengass: I think very important is to know, even though we tell the patients this is not curable, it is a very treatable disease. It is a disease where you can live with a good quality of life. That is very important, to know, because obviously, I mean, I would be devastated if I heard the word cancer and multiple myeloma is not a very common one.

So oftentimes people are just confused. What does that even mean? Like, why multiple and why myeloma? What, what does that mean for me? I think it's important to know we can treat very well our goal. But I think we hopefully can treat at the first step might be we can treat patients long enough and keep them alive long enough that they pass away from old age and not pass away from their myeloma.

We don't always achieve that, but that is one of the goals we have and then eventually we want to come to a point where we can really cure the disease so that it's gone and gone forever. This is what we are aiming for. And I think I have overseen the last decades of myeloma research and there have been such tremendous changes in this disease and how we diagnose and how we treat it that I'm very hopeful that at one point we will come to the point that myeloma is not really that devastating anymore, and I can have different discussions with my patients.

Pathak:Thank you again to Dr Hillengass for demystifying multiple myeloma and helping us understand the innovations in treatment and research from exploring diagnostic challenges to highlighting cutting edge therapies Like CAR T cell treatments, we've learned how a once largely untreatable condition is quickly evolving into a far more manageable and in some cases almost undetectable disease.

I'm particularly excited by the lifestyle interventions that not only play a role in helping with other chronic conditions someone might have, but actually, potentially helping to manage the cancer itself. But patient care isn't just about medical breakthroughs.

It's also about the day-to-day support and practical advice that can help people live their fullest lives with myeloma. In this next segment, we're joined by Jacqueline Henry, the nurse manager for the lymphoma and myeloma department at Roswell Park. With many years of experience coordinating patient care, Jacqueline knows firsthand the struggles and concerns myeloma patients face.

Especially around quality of life, maintaining hope, and managing the emotional weight of a chronic disease. If you've ever wondered, is there still a reason to fight when there's technically no cure or how to balance doctor's visits with real life, Jacqueline's insights will offer clarity and encouragement. So let's dive in.

Jacqueline Henry, BSN, RN:When I hear a patient say, there's no cure, what's the point, or there's no cure, I have no hope, I remind them that there's a lot of diseases that we don't have cures for, that we manage pretty well, and that's what we're hoping to do with our myeloma patients, so we hope for this to be a success. disease that they are able to live with and live with meaningfully as we treat them through the entire spectrum from active treatment to more long-term management and many people are going to have a pretty good quality of life through the treatment and I remind them that it's like a patient who has diabetes.

You might always have diabetes or heart disease. You might always have heart disease, but we can manage those things and we can still give you great quality of life.Our patients tend to be on the older end of the spectrum, so 60 and above. We have patients who are generally male, and so what quality of life looks like to them is what they think quality of life looks to them.

So we talk a lot about treatment goals. What is it that you want to achieve? What does a happy, healthy life look like to you? You're going to have this disease. It's going to live with you forever, but we can make sure that you're eating healthy. We can make sure that you're exercising moderately and in a safe way.

We can make sure that you're able to see your family go through milestones. Maybe you have children that can grow up. You have grandchildren that can grow up. Graduations. birthdays, anniversaries. That's the kind of thing that we're trying to achieve is to give you more time to get to those more lifestyle important things for people. So quality of life is what the patient thinks it is.

Quality of life looks a lot different for our patients. I like to have a discussion with our patients about what their next six months looks like and what their next year looks like and what living with myeloma looks like. So I have a discussion with him about what the time requirement is. for all of those time periods and what life at home would look like.

Part of that is asking them what their home is like. do you need more help at home, do you think? Do you have pets? Do you have access to healthy food? Because I think that most, people, aren't asked that, so they don't think about it, but we do want to focus on healthy food. And can you take walks?

We talk about exercise a lot with myeloma at Roswell, and one of the things that we strongly encourage is when the weather permits, is that you take a walk, because that's a low impact activity that actually really helps people to be better. I recommend that they find something that they enjoy picking up a hobby that isn't high impact, that doesn't require a lot of energy, and that they can pick up and put down whenever they want.

I encourage patients to have a journal because as you go through your day, you're going to find that you have questions for the doctor that you may not remember at the time of the visit, or in a doctor's visit, there's a lot of segues that happen. This allows you to redirect the conversation back to the questions that you had, so you leave that visit with all of your questions answered

 If I were to talk to somebody who is struggling to find hope after their diagnosis, I would tell them, you're not alone in feeling that way. I think that that is Not an unexpected way to feel, and I think that you find things in your life that you enjoy, the people in your life that you enjoy, creating a sense of community, those people, those activities and those things will be what carries you through some of the toughest times, and this is coming from patients.

We have a lot of ways that they can connect with other people with their disease as well, because. I can be empathetic and sympathetic, but I can't experience what they're experiencing. So I want them to talk to other people who have been through it. So perhaps they're talking to somebody who's been living with myeloma for years and years and years and getting that aspect and we do that through support groups.

We also have, a program where they can meet up with somebody who has had the disease, the same disease as them, and they can talk to them about their specific concerns, and they find most people who go through this disease are encountering the same thing, so there's a sense of comfort in that, so that they're not the only ones going through this, but it's understandable. that you're feeling the way that you feel and to, to give validation to that. 

Pathak:My conversation with Dr Hillengassand Jacqueline Henryreally highlighted the complexities of multiple myeloma. He emphasized the importance of early detection, noting how common symptoms like persistent and worsening back pain are often overlooked or attributed to other ailments. Multiple myeloma is frequently preceded by smoldering stages, stressing the need for more awareness.

even in younger patients who might experience delayed diagnoses. Dr Hillengass shared valuable insights into the latest treatment options, including CAR T cell therapy, drugs, and bio specific antibodies, innovations that have significantly improved survival rates and quality of life.

Equally important, both my guests share an optimistic outlook, illustrating the rapid progress in research and the hope that one day multiple myeloma may be cured altogether, to find out more information about Dr Jens Hillengass and Jacqueline Henry, please visit our show notes. Thank you so much for listening. Please take a moment to follow, rate, and review this podcast on your favorite listening platform. If you'd like to send me an email about topics you're interested in or questions for future guests, please send me a note at [email protected]. This is Dr Neha Pathak for the WebMD Health Discovered podcast.