Listen and followApple PodcastsSpotifyYouTubeMore apps · Browse all episodes
This article is sponsored by Loxo@Lilly, the oncology unit of Eli Lilly and Company.
In this special sponsored episode from Loxo@Lilly, I’m joined by Dr. John Pagel, senior vice president of clinical development and global head of hematology at Loxo@Lilly, to discuss blood cancer — what it is, advancements in research and treatment, and his experience in the field.
There are an estimated 1.5 million people in the U.S. living with leukemia and lymphoma, which are types of blood cancer.
In leukemia and lymphoma, white blood cells behave abnormally, and the maturity of these cells determines the type of disease. Abnormalities in immature white blood cells cause leukemia, and abnormalities in mature white blood cells cause lymphoma.
“Somewhere in that process of cell maturation, something can go wrong,” Dr. Pagel says. “They start making too many of themselves. I always think of this like when those white stormtroopers in Star Wars all march.”
Mantle cell lymphoma
There are close to 80 subtypes of leukemia and lymphoma. Mantle cell lymphoma (MCL) is a form of non-Hodgkin lymphoma that arises from a type of white blood cell called B lymphocytes. It is a rare blood cancer that affects the lymphatic system, which helps protect the body against infection and disease.
“Mantle cell lymphoma is one of the more interesting subtypes of non-Hodgkin lymphoma that we address and think about,” Dr. Pagel says. “It has often behaved very aggressively. It is true that people often get chemotherapy for this lymphoma early on, and they get to remission, and they might do well, but they typically will relapse.”
Because relapse is almost universal for people with MCL, many patients will require several lines of treatment. Dr. Pagel says that fortunately, providers now have “a lot of arrows in our quiver of tools” to manage MCL due to recent advancements in research.
There are various approaches to treating MCL, including immunomodulatory and cellular therapies. Inhibition of Bruton tyrosine kinase (BTK), an enzyme that is essential for the normal lifespan of a white blood cell and critically important for the survival of cancerous cells, is also an option. In simplified terms, when cancerous cells grow and divide in MCL, Dr. Pagel says, it is like a light switch has been turned on that won’t turn off. But inhibiting BTK, that critical protein, is one way to address that stuck light switch.
Challenges — and rewards
Although the MCL treatment landscape has grown in recent years, there are still challenges that physicians face in treating and researching this disease and other blood cancers.
Dr. Pagel says that when treating patients, the biggest problem is getting the right therapy to the right person at the right time — so it is critical that patients speak up and find a physician they trust and respect.
“Patients need to be their own best advocate,” Dr. Pagel says. “Do your research, look at your options, talk to your doctor, ask hard questions.”
In terms of hurdles in blood cancer research, Dr. Pagel says that the development of novel therapies can be extremely challenging.
“This process takes a lot of time,” Dr. Pagel says. “Time from discovery of a drug to approval and on the market can take a good decade depending on the drug and depending on the disease.”
Despite the obstacles Dr. Pagel has witnessed in addressing blood cancers, he says he has been lucky to also experience positives over his 25-year career as a physician and researcher, including the special relationships and impact he has been able to have with patients facing life-threatening illnesses.
“People will often ask, ‘How could you go into this field? It’s so depressing, and it’s hard.’ It’s actually completely the opposite,” Dr. Pagel says. “This profession has allowed me to help patients at a level that is really hard to find in any other profession. I’m super lucky and fortunate to have had that kind of opportunity to do that.”
John Pagel is a hematology-oncology physician and senior vice president of clinical development and global head of hematology, Loxo@Lilly.
VISIT SPONSOR → https://www.loxooncology.com/
SUBSCRIBE TO THE PODCAST → https://kevinmd.com/podcast
RATE AND REVIEW → https://kevinmd.com/rate
FOLLOW ON INSTAGRAM → https://www.instagram.com/kevinphomd
FOLLOW ON TIKTOK → https://www.tiktok.com/@kevinphomd
Transcript
Kevin Pho: Hi, and welcome to the show, where we share the stories of the many who intersect with our health care system but are rarely heard from. Subscribe at kevinmd.com/podcast. Today we have a special sponsored episode from Loxo@Lilly. We welcome Dr. John Pagel, senior vice president of clinical development and global head of hematology at Loxo@Lilly, bringing 25 years of experience as a physician treating patients on the front lines to a passion for researching treatments for blood disorders, including lymphomas and leukemias. Throughout his career, Dr. Pagel has served as a principal investigator of numerous protocols and has been involved in several other clinical trials. Today we’ll be discussing blood cancer seen through the lens of a researcher. John, welcome to the show.
John Pagel: Great to be with you, Kevin, and great to be with your audience. You’re speaking to me about a subject that’s really near and dear to not only my career but my heart, so thanks for the opportunity.
Kevin Pho: So John, can you briefly share a little bit about your story and your current role at Loxo@Lilly?
John Pagel: Oh, yeah, sure, of course. We all have a story. My story was an endeavor into blood cancers way back when I was a medical resident, which was in the mid-1990s. I’m dating myself, unfortunately; I guess the gray hair does that too, sorry. But at that time, I was really, really becoming very interested in the science around blood cancer therapies and how we can help patients with novel treatments. Remember, not that long ago, the only thing that we had for patients, not just patients with lung cancer or colon cancer but blood cancers too, was a handful of chemotherapy agents. That’s all we used, and it was difficult on patients.
Just around that time, when I was a medical resident, there was the idea of targeting blood cancer cells with a biologic therapy, and in particular antibody-based therapies. We make antibodies in our own body, of course, primarily to fight infections. Those antibodies target bacteria or viruses or what have you. Well, at that time, we were just starting to get into this idea that we could make these antibodies in the laboratory and that we could make them to target a cancer cell. I was very turned on by the idea of actually using something that’s not chemotherapy, and I started to go and look for an opportunity to do blood cancer research around these kinds of new, novel targets or therapeutics. That kind of started a whole career of really developing drugs, primarily in an academic setting and now more recently at Loxo@Lilly, that are not chemotherapeutic agents.
Kevin Pho: So tell us what makes you so passionate about blood cancer research and working in the hematology space.
John Pagel: Yeah, I think this is a really incredibly unique field, and I’m lucky that I’ve been able to be part of it, a small part, of course. I think the most important thing to recognize, as a big picture, is that with the therapies we have and the drugs that we’ve developed and continue to develop, we’re really, really helping people. We’re helping patients who have life-threatening illnesses. As an example, when I first started in this field, Hodgkin lymphoma was a lymphoma that killed more patients than survived the therapy. It is rare now for someone to die of Hodgkin lymphoma, and that’s simply because of the research that has been done, and the opportunities that have been able to be explored have been game-changing. That attracted me to this field, so I have been lucky enough to be part of those kinds of events in my own small little way.
Kevin Pho: Can you explain what causes B-cell lymphomas?
John Pagel: Yeah. Like every cell in our body, these cells have a job to do, and blood cells have a job to do. Of course, people well understand that red cells carry oxygen. There’s a blood cell called a platelet that’s very important for blood clotting. But the majority of our blood cells are white blood cells, and their normal job is to keep us happy and healthy, to fight infections, and to keep us off of our sickbed. It is true that with any cell, something can go wrong in the process of how these cells develop and grow and divide. In many ways, it’s just a random process. Sometimes, of course, there are external influences, and we can talk about what could drive these things. But something goes wrong in the machinery of the cell, and when it happens in white blood cells, it leads to diseases where those cells behave abnormally, and in fact it might be something we call a leukemia or lymphoma.
To describe that a little more, Kevin, if you don’t mind, I’d just say that these white blood cells are born in what we call the bone marrow, the long bones of our legs or arms, the ribs, the skull. That’s where these cells come from, and they’re born there. Just like maybe your kids or my kids when they were younger, they grow up. These cells become adolescents, and it’s time for them to leave the house. They leave the marrow, they start circulating in the blood, and they’re looking for a profession. Of course, their profession is to fight an infection, so they went to school for that. And they’re looking for a home, and they like to live in what we call lymphatic tissue, so those are lymph nodes; the spleen is just like a big lymph node. These cells hang out there until they do their job. When they’ve done their job, which is again to fight one of those infections, those cells go on to become grandparents, and then they die, and then the next cells come along and do their job. That process just routinely happens.
But again, as I’ve said, somewhere in that process of cell maturation, something can go wrong. It depends on where it happens, where something goes wrong, meaning that there’s an error made and that cell gets, again like my kids have been, arrested in its development. That leads to a cancer, a blood cancer. So if they get arrested in their development early on in that maturation phase, those cells now stop maturing, and I always think of this like those white stormtroopers in Star Wars all marching; they all look exactly the same. Again, if that happens in an immature cell, that leads to diseases we call leukemias. If that white blood cell happens to be a very, very, very mature cell, and it more often happens that way, we call it a lymphoma. And every step in between will lead to a different subtype of these blood cancers. In fact, I think there are somewhere close to 80 different subtypes of lymphomas and leukemias, so it’s not just one disease when we say blood cancers. That’s kind of the big story of how these cells become cancer cells, and hopefully everybody followed that.
Kevin Pho: Knowing non-Hodgkin lymphoma is the most common form of lymphoma, can you speak a little bit about the difference between Hodgkin lymphoma and non-Hodgkin lymphoma?
John Pagel: It’s a really important point, and it often confuses a lot of people. Hodgkin lymphoma and non-Hodgkin lymphoma are two totally different things. They’re like apples and oranges. Yeah, they have the word “lymphoma” attached to them, but the mutations that lead to the arrested development, the clinical characteristics, and how this plays out in patients are extremely different. Hodgkin lymphoma typically happens in young adults, so this is the 20-year-old who is off to college and feels a lymph node. That’s a disease that’s rarely seen in adults of advanced age, although you can see a little bit of a peak in people in their 60s getting Hodgkin lymphoma. And then everything that’s not Hodgkin lymphoma is what we call non-Hodgkin lymphoma, and again, that’s where the 80 different subtypes come in. I’ve mentioned some of those words: follicular lymphoma, large cell lymphoma, mantle cell lymphoma. Those are just non-Hodgkin lymphomas.
Kevin Pho: So can you talk a little bit more about one of the subtypes of non-Hodgkin lymphoma, mantle cell lymphoma, and whom it affects the most?
John Pagel: So mantle cell lymphoma is just one of the more interesting subtypes of non-Hodgkin lymphoma that we address and think about, and it’s interesting on lots of levels. We know that this lymphoma occurs because there are parts of two different chromosomes that break off and rearrange. There’s a part of chromosome 11 that breaks off and part of chromosome 14 that breaks off, and those two pieces actually come together. When that happens, it leads to a disease we call mantle cell lymphoma. It’s not tremendously common; it actually only makes up maybe about 5 percent of all non-Hodgkin lymphomas. It has often behaved very aggressively. It is true that people often get chemotherapy for this lymphoma early on, and they get to a remission, and they might do well, but they typically will relapse.
The beauty of treating patients with mantle cell lymphoma, on the provider side, is that now we have a lot of arrows in our quiver, tools in our toolbox, of what we can use for mantle cell lymphoma patients. Actually, now we’re seeing people who are living with mantle cell lymphoma for 15 years, 20 years. Again, this is also recognizing the fact that this is primarily a disease of people who are a bit older, so these people have median ages where they get diagnosed in their mid- to late 60s, or even 70s, maybe even 80s.
Kevin Pho: What are some of the common symptoms associated with mantle cell lymphoma? And briefly share some of the challenges with the disease.
John Pagel: Yeah, I think one of the most important things to understand about this lymphoma is that people often will present sick. They will very commonly have widespread systemic disease, in other words, multiple lymph nodes, and large ones. Remember, these cells like to live in lymph nodes, and when something goes wrong there, they again get arrested in their development, they start making too many cells, and of course then the lymph nodes get bigger and bigger, and they don’t feel good. So they can be having fevers, sometimes drenching night sweats. And by the way, we all have these night sweats. What we’re talking about when your doctor says drenching night sweats is that you’re soaking the sheets, not just once in a while, but every night. You might be losing weight; your body weight is dramatically falling off despite the fact that you’re eating well. These people often need attention and therapy relatively quickly.
Kevin Pho: Can you talk a little bit about BTK inhibition and why it is important for mantle cell lymphoma patients?
John Pagel: So this is really one of those reasons why I was attracted to having a career in blood cancer research and treating patients with blood cancers. Bruton tyrosine kinase is an enzyme that’s critically important for the survival of these cancer cells. In our cells, we have all this machinery. They’re proteins, or we also call them enzymes, proteins that are important for the normal functioning of the cell, and that protein, BTK, is important for the normal lifespan of a white blood cell. But something can go wrong in that cell where, you can think of it this way, Kevin, the light switch has been turned on, and you can’t get the light switch off. So the cell is just continuing to grow, divide, and make more of itself. Often what we’re going to do is try to turn that light switch off, but in this case, that light switch is stuck. So the other way to turn the cell off is to cut the wire, and the way we cut the wire is we target that critical protein, Bruton tyrosine kinase, or BTK, that’s inside the lymphocyte.
Kevin Pho: What challenges do physicians face working in the blood cancer space?
John Pagel: Oh, boy, I could give you a whole podcast on that. Well, listen, there are lots of different challenges, and you can look at them as to whether they’re on the treating physician’s end or on the drug development end. I’ll give a little perspective about both, since I’ve spanned all that. On the patient-treating side, the biggest problem that we have is getting the right therapy to the right patients at the right time. That comes back to one thing I always say, and I haven’t said it yet here, but I’ll say it now: Patients need to be their own best advocate. They are the best advocates for themselves. Do your research, look at your options, talk to your doctor, ask hard questions. Physicians are never offended, in my experience, by second opinions. They’re never offended by you bringing them ideas and other things to explore. Often, of course, physicians who are taking care of patients have a better handle on this than the patient themselves, but speak up nonetheless. As a patient, speak up for what you’re curious about, what you want to know about, what your options are.
Now, the other end of this, of course, is the development of novel therapies, new therapies for patients, which is extremely challenging. We do a pretty good job in this way across the board, but you also have to remember, of course, that this process takes a lot of time. The time from discovery of a drug, through patients, to actually approval and on the market can take a good decade, sometimes, depending on the drug, depending on the disease. So the challenges of developing drugs for these diseases are extremely big, and we need to continue to support that. We can do things well for patients, and we can do things well for pharmaceutical companies or researchers who are developing these drugs. We just have to figure out a better way to do it.
Kevin Pho: As a physician, what obstacles do you see most often that patients have to overcome in their journey with mantle cell lymphoma?
John Pagel: Yeah, that’s a really interesting question. I think the obstacles are unique and perhaps somewhat different for each individual patient, but it’s a commitment. It’s a commitment to care. You need to find a physician that you trust and respect, where there is mutual trust and mutual respect, and if you’re not finding that, you need to continue to look. Often it’s hard to do all these treatments, or any of this, all by yourself. You certainly need support, not just from a caregiver, but sometimes even financially. I will just say, explore financial help that companies provide, or that foundations for cancer provide, and actually explore those opportunities, like the Leukemia & Lymphoma Society and the Lymphoma Research Foundation, these important organizations that help patients address the challenges. That might be rideshares to the doctor’s office, which are plentiful if you go find them and get them.
Kevin Pho: And what are the most important things clinicians should understand about mantle cell lymphoma?
John Pagel: Well, yeah, listen, I could go on for a whole podcast on that too. The most important thing is to understand that if something is not going well, listen to that patient and do something different. A lot of times, of course, we can separate ourselves as physicians from the patient and not know exactly what that patient is going through. We might hear the words, but they don’t really touch us or resonate the way they’re touching and resonating in that individual patient. So I guess, Kevin, this comes back to my point around physician-patient interactions. It’s mutual respect, it’s working together, it’s a two-way street, and that’s critically important for the best outcomes.
Kevin Pho: You’re listening to a special sponsored episode of The Podcast by KevinMD. Our guest is Dr. John Pagel, senior vice president of clinical development and global head of hematology at Loxo@Lilly, bringing 25 years of experience as a physician treating patients on the front lines to a passion for researching treatments for blood cancers, including lymphomas and leukemias. John, what are some of your proudest accomplishments as a researcher?
John Pagel: Well, listen, I think there are a lot of things that are near and dear to my heart that I am proud of that we can talk about, but I think the biggest thing I can say, without question, is the impact and the special relationship with patients who have life-threatening illnesses that I’ve actually been lucky enough to experience. People will often ask, Kevin, “How could you go into this field? It’s so depressing, and it’s hard.” And it’s actually completely the opposite. This profession has allowed me to help patients, and to connect with patients, at a level that is really hard to find in any other profession. I’m super lucky and fortunate to have had that kind of opportunity to do that.
Kevin Pho: How would you describe the role Loxo plays in the blood cancer treatment space?
John Pagel: Yeah, listen, I’m very proud of what we’re doing here at Loxo@Lilly in blood cancer research. We are growing our blood cancer portfolio. Our approach is to focus not always on the biggest drug, or what have you, but on drugs that make a big difference for patients. We are always willing and wanting to tackle the difficult problem.
Kevin Pho: Two-part question next: What is a message you would like to give to blood cancer patients, and what is a message that you would like to give to clinicians?
John Pagel: Well, my first answer, to the patients, is never give up hope. There are tons of clinical trials out there in blood cancer research that might be appropriate. There are many trials that might be appropriate for each individual patient, and some might have multiple options for trials. Don’t shy away from getting involved in trials, even what we call early-phase trials. People do make shifts in their care from involvement in these trials. So don’t give up hope. Hope is critically important, and it’s there. It’s real, it’s tangible, and I know that it makes a difference if you can continue to think about it and look at it that way.
And then for physicians, I think it’s kind of the same thing. I learned a long time ago that I need to listen to my patients about what needs to be done next much more than I probably need to tell them what needs to be done next. I can tell you about times when I’ve heard from patients that they don’t want to stop treatment when I thought that maybe they should, and I was wrong. I was wrong. So physicians shouldn’t lose the hope, and they should listen to patients. And I think, really, across the board, that’s what oncologists, cancer doctors in particular, do. They’re all in it for the patient. There’s no other way to do this profession, in my opinion, if you’re not all in it for the patient.
Kevin Pho: And my last question, John: Just share some take-home messages that you want to leave with the KevinMD audience.
John Pagel: Yeah, and listen, I think you hear from me my enthusiasm for what’s been done, but I hope you also hear that enthusiasm for what’s coming. We now have drugs that I hadn’t ever even dreamed of thinking about 25 years ago. So, bringing it all full circle, I think let’s all continue to really engage, be actively involved, continue to maintain hope, and really provide outcomes for our patients.
Kevin Pho: You’ve been listening to a special sponsored episode of The Podcast by KevinMD. Our guest was Dr. John Pagel, senior vice president of clinical development and global head of hematology at Loxo@Lilly, bringing 25 years of experience as a physician treating patients on the front lines to a passion for researching treatments for blood cancers, including lymphomas and leukemias. John, thank you so much for sharing your perspective, time, and insight, and thanks again for coming on the show.
John Pagel: It’s been great, Kevin. It’s really nice to be with you. Thanks for having me.
Listen and followApple PodcastsSpotifyYouTubeMore apps · Browse all episodes
