World Cancer Research Day With Samuel Kareff, MD, MPH; Maria Badillo, RN; Matthew Hadfield, DO; and Alankrita Taneja, MD

Oncology Data Advisor: Hi everybody, welcome to Oncology Data Advisor. I'm Keira Smith. I'm the Senior Editor at OncData, and today, we're really excited to be hosting this panel discussion in honor of World Cancer Research Day.

I have the pleasure of being joined by a few members of our Fellows Forum and Editorial Board. We have Dr. Samuel Kareff, who is the Chief Hematology/Oncology Fellow at the University of Miami Sylvester Cancer Center. We have Maria Badillo, who is the Research Nurse Manager in the Mantle Cell Lymphoma/Myeloma Department at the University of Texas MD Anderson Cancer Center. And we have Dr. Matthew Hadfield, who is a Medical Oncology Fellow at Brown University.

Thank you all so much for coming on today. I'm really excited to have this discussion and shed some light on World Cancer Research Day. To start off, a good intro question for everybody is, would you like to each introduce yourselves and share a little bit about the area of cancer research that you're most passionate about? Dr. Kareff, we can start with you.

Samuel Kareff, MD, MPH: Thanks so much, Keira. Thanks for the panelists for their time, as well, and for everyone joining the livestream. My name's Dr. Sam Kareff. Like Keira mentioned, I'm down here in South Florida. Something that's become of interest to me over the past few years, and what I've seen clinically, especially during my training in hematology and oncology, is the effects of air pollution and how they relate to lung cancer.

Just a few hours ago, Professor Charles Swanton from the UK was delivering the keynote address at the LUNGevity Survivorship Conference, where he was discussing a new mechanism that he and his researchers have found for particulate matter 2.5 and how it leads to a specific type of non–small cell lung cancer called epidermal growth factor receptor factor (EGFR)–mutant. This is something that's very alarming, obviously, given the climate change that we're experiencing. Just this week in the news, we saw that the progress the US has made in terms of air quality has been completely erased and perhaps reversed by the increase in wildfires we're seeing throughout the continent and globally. This is something that I'm really hoping we can study moving forward, and something that I think panels like these are wise to address and call for more research and funding.

Oncology Data Advisor: Great. Maria?

Maria Badillo, RN, MSN, OCN^®, CCRP: Good afternoon, Keira; good afternoon, panelists; and good afternoon, everyone. My name is Maria Badillo. I work as a Research Nurse Manager. I have been working in clinical research for the past 15 years. I work with lymphoma and myeloma clinical trials, mostly focusing on mantle cell lymphoma, which is one of the rare types of lymphoma.

Oncology Data Advisor: And Dr. Hadfield?

Dr. Hadfield: Thank you, Keira, and thank you to both of you for the great introductions. It's great to be a part of this panel. My name's Matt Hadfield. I'm currently a third-year Medical Oncology Fellow at Brown University in Providence, Rhode Island. Predominantly, my research interests are in early-phase clinical trials, so phase 1 clinical trials, mostly centered on new medications that overcome immunotherapy resistance and novel immunotherapeutic combinations. My big area of interest, dovetailing off that, is immunotherapy toxicities.

We currently don't have very good biomarkers to predict who's going to develop immunotherapy toxicities, and unfortunately, our way of managing immunotherapy toxicities is still pretty crude, relying a lot on high-dose steroids and very small-scale studies. As we see more and more immune checkpoint inhibitors used in the neoadjuvant setting, I think it's going to become more and more pertinent to a wide array of patient populations, both in solid tumors and hematological malignancies. I hope to work on more projects related to identifying which patients develop these toxicities, hopefully leading to better outcomes for cancer patients.

Oncology Data Advisor: Awesome. These are all such important areas of research, and I'm looking forward to hearing more about your work in these fields and the progress that's occurred recently. Dr. Kareff, if you'd like to start on our next talking point, what progress has recently occurred in this area that you're researching, and what progress are you looking forward to seeing in the next year or so?

Dr. Kareff: Absolutely. In addition to the context that we discussed, what's really been remarkable is this new mechanism that's been proposed by the group I mentioned a few minutes ago. Essentially, what they found is that specific error pollutants that constitute particulate matter 2.5 can induce specific forms of inflammation at the cellular level. This is what perhaps drives this unique subset of non–small cell lung cancer, the EGFR-mutant disease, like I mentioned a few moments ago. What's exciting is that we've now seen this link. What is alarming is that there are changes that are continuing to happen, that we need to help not only prevent in the future, but also make sure that this is seen in a worldwide fashion.

What do I mean by that? The majority of the work that we've seen so far has come from cohorts specifically in Europe, especially in the UK, as well as Southeast Asia. Now, we do know that particulate matter levels vary worldwide, and they may be linked with specific emitters of particular matter, like diesel, coal, and that sort of thing. One of the things moving forward that I'm actually hoping to study, in addition to my collaborators at the University of Miami, is looking at that mechanism from the North American perspective. I think that would be really interesting, both in validating the hypothesis, but also potentially paving the way for chemoprophylaxis. It would be great if you could imagine either intravenous (IV) or oral treatments that prevent lung cancer before it starts.

Ms. Badillo: For me, when I started working in clinical research at MD Anderson in 2008, there were very few drugs approved for mantle cell lymphoma. The standard-of-care treatment was chemotherapy with or without stem cell transplant. Over the years that I've worked in clinical research, our team has been very fortunate to see six drugs get FDA-approved, mostly oral drugs and one chimeric antigen receptor (CAR) T-cell therapy. Right now, our team is very, very excited. We've been seeing the advent of new treatments, such as bispecific antibodies, trispecific antibodies, and other new CAR T-cell therapies. These are very promising for our patients. I also want to touch on the value of the clinical team. I'm really passionate about the new tools that we can use for our patients in order for it to be easy for them to participate in clinical trials.

Dr. Hadfield: As I mentioned, immunotherapy toxicities is an area that's very interesting to me, and something that I think we're going to have to spend a lot more time thinking about and critically looking into predictors of who's going to develop toxicities, particularly as these therapies start to trickle down into the neoadjuvant setting. To Maria's point, there are a lot more novel adoptive cellular therapies that are coming in the future, like CAR T, and natural killer (NK) cell–based therapies. As we start to explore these therapies more, as we gain an efficacy, we're going to have to manage the toxicity and really make sure that appropriate patient selection is at the forefront of making clinical decisions.

So far, there hasn't been a ton of advancement in terms of predicting, particularly in the context of immune checkpoint inhibitors, who's going to develop toxicities. There was a very interesting study recently that was published at Massachusetts General Hospital (MGH) that showed that certain human leukocyte antigen (HLA) subtypes could potentially predict who may or may not develop a toxicity. An interesting study published by a group at the University of Texas (UT) Southwestern just a couple of weeks ago showed that T-cell binding capacity could also be a potential predictor of who may or may not develop toxicity. But we're very, very early on in terms of those types of predictive biomarkers and aiding in patient selection criteria.

In terms of managing immunotherapy toxicities, we know from large retrospective cohorts in melanoma that steroids do reduce efficacy. You can imagine, if you're giving a drug and its whole purpose is to take the brakes off the immune system and to fight cancer shells, that giving large doses of immunosuppressive medications is going to hinder that to some degree. We see that retrospectively. But there are some very interesting novel preclinical models with blocking tumor necrosis factor (TNF) alpha and interleukin-6 (IL-6) that show that you can actually preserve the efficacy of an immune checkpoint inhibitor while uncoupling it from the immunosuppressive nature of treating an immunotherapy toxicity. But we're very, very early on in those and there are not a lot of trials currently underway, so it's an area that we really need to explore further in the future.

Oncology Data Advisor: Hi Dr. Taneja, thanks so much for coming on today. To catch you up to speed, would you like to introduce yourself and then share an area of cancer research that you're most interested in or particularly passionate about?

Dr. Alankrita Taneja: Thank you for having me. I'm Alankrita Taneja. I'm one of the Fellows from Roswell Park Cancer Institute in Buffalo, New York. One of the areas of cancer research that I'm really passionate about is the prevention of progression to multiple myeloma in patients with precursor states such as monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma. There are a lot of experts in the field who are looking at different modalities through which we can do this. There were some major trials recently presented, like the ASCENT trial, which looked at chemotherapy to cure smoldering multiple myeloma so that these patients do not progress to multiple myeloma at all, in the hope that we can improve outcomes for patients with plasma cell disorders.

More interestingly, some experts in the nation are also looking at some complementary and alternative modalities that are shown to slow this progression. For example, there've been studies called the NUTRIVENTION-1, -2, and -3 trials from Memorial Sloan Kettering (MSK) that are looking at plant-based diets and supplements in patients with MGUS and smoldering multiple myeloma. Some of these trials include obese patients, and they're trying to see how intervening with whole-food, plant-based diets, as well as dietary counseling, can reduce inflammation in these patients. Some more data will be presented at the International Myeloma Society (IMS) Annual Meeting by Dr. Urvi Shah this coming week, wherein she's showing that it's also slowing the progression from MGUS smoldering to myeloma.

Similarly, we have some studies from Roswell Park where we've seen that using exercise in patients with precursor states is actually increasing the T-cell repertoire to a more non-exhaustive kind of profile, which implies that these T cells are more active and more able to fight against precursor state myeloma cells but still limit their progression to multiple myeloma. I think it's a difficult patient population to study, MGUS and smoldering, just because the progression is really slow. Most patients with MGUS progress at the rate of 1% per year if they're low-risk. Smoldering patients do progress faster than that, but it's still very difficult to really capture those patients who are going to progress in the next few years. Studying these modalities in these patients is something very exciting that we are trying to look into more.

Oncology Data Advisor: Awesome, it's definitely a really important patient population to study. We've had the pleasure of talking with Dr. Shah about the NUTRIVENTION studies a few times before, and it's very interesting work, so we're looking forward to hearing more about that.

Dr. Taneja: Yes, and I'm really excited to see her latest research on what exactly the progression is. So far, she's looked at the microbiome and seen how butyrate levels and surrogate markers of disease progression are increased in patients following plant-based diets. But in the upcoming meetings, she's actually going to talk about the myeloma markers and how myeloma progression is delayed in these patients, so I'm looking forward to that.

Oncology Data Advisor: The next question for everyone—and Dr. Kareff, if you'd like to start—are there any messages you'd like to share about the area of research that you focus on to raise more awareness of it in light of World Cancer Research Day?

Dr. Kareff: Yes, absolutely. I think there's one clinical take-home, and then one human take-home. The clinical take home is that the face of lung cancer is changing before our eyes. It's quite remarkable. When I talk to oncologists from a couple of generations of training beyond us, I'm hearing that so many younger patients and so many more women are being diagnosed with lung cancer. It's almost like there's an epidemic happening. As we try to understand why, I really call for all institutions, researchers, and providers who are interested in this topic to try to make a mark and understand what's going on. Like I mentioned, I believe air pollution is one of these drivers, and I hope I can understand that a little bit better in our continent.

On the human side, and this can be discussed at length in another setting, I really think we all need to try to contribute to halting climate change. We just heard at the United Nation (UN) General Assembly during Climate Week that this is really an emergency in our generation and for those beyond. I urge everyone to not only take a look at their individual lives and see how they can help mitigate that, but also to appeal to their policymakers and other sorts of legislators to try to make an impact here.

Ms. Badillo: For most of my career as a nurse, I've worked in clinical trials, so I know some patients are very uncertain, hesitant, or doubtful if they hear about clinical trials or if their physician offers for them to enter a study. I encourage our patients to ask questions. Don't be afraid to reach out to your doctor, study nurses, or coordinators, especially if there are questions that were not addressed during your visits. Actually, most of our patients are very grateful to participate in clinical trials because they can have access to these new treatments even before they get FDA-approved. Clinical teams such as your doctor, your nurses, and your coordinators are here to guide you and will help navigate any logistics or any protocol questions you may have. Definitely, like I said, it will enable you to have access to a treatment before it's FDA-approved.

Dr. Hadfield: Absolutely, and I just want to echo that the conversation has been so wonderful so far. We think about diagnosing cancer and we think about treating cancer, but when we start talking about air pollution and how that may impact the development of lung cancer, or how exercise may prevent the development of myeloma, you really start to see the holistic approach to cancer care. Really, it shows how we're all interconnected, and how Maria talks about the clinical trial teams and how they're so integral to treating patients. It's great to hear.

With regards to immunotherapy toxicities, I can't say enough that I really think everyone's going to care a lot more about these as they trickle into the neoadjuvant setting. I think as we start to see unfortunately, and we've all seen it before, patients develop immunotherapy toxicities and then that takes away a potentially life-saving treatment. That's devastating, and it stays with you for a long, long time. You never forget it. The concept that we need predictive biomarkers to determine who's going to do well and who's going to do poorly with regards to toxicities is really important right now.

I would also echo that I think immunotherapy toxicities are not something that just oncologists manage. Everyone has to have a high clinical suspicion for diagnosing these types of toxicities—primary care physicians, hospitalists, surgical subspecialties, really every subspecialty. Everyone sees these, and we all have anecdotal stories of how they've gone missed or misdiagnosed and patients didn't get steroids fast enough. This is an area that's really exploding with all the FDA indications with regards to immune checkpoint inhibitors, and I would hope to just raise awareness that it's a really important issue that we're all going to have to deal with.

Dr. Taneja: I would just like to echo everyone's thoughts here about how we should think bigger and look at the bigger picture when it comes to preventing and reducing the progression of cancer. More and more, we are looking at complementary modalities being used. In the past, we generally believed that these were not really affecting the cancer per se, but sometimes it would help with the side effects from treatment or just coping with treatment, such as using stress reduction modalities to provide support and things like that. But more and more, we are now investigating whether things like diet, exercise, and stress reduction are affecting the progression of cancer at the cellular level and at the immune level. I think patients should ask their doctors more about these in adjunct to their chemotherapy and other treatments that they're getting, so that they can not only feel better but also maybe have a chance to reduce the progression of their cancers.

Oncology Data Advisor: Absolutely. As we wrap up, any parting words any of you have or anything else you'd like to mention?

Dr. Kareff: If you don't mind, I just really want to compliment my colleagues here. I'm feeling really enthused by their research directions, as well, whether it's from the clinical trial side or toxicity management or my favorite field, prevention. I think this is just wonderful work you're doing. I congratulate you, and best of luck to you all.

Oncology Data Advisor: Thank you all so much for coming on this panel today and telling us about your passion for cancer research, your efforts in this field, and all the ongoing efforts by everyone else. It's definitely inspiring to hear about the progress that's occurred and that's expected to occur in the near future. Thank you to everybody for watching this discussion. We really appreciate you joining in today. Be sure to follow Oncology Data Advisor at OncData.com, as well as on YouTube and Twitter, for more oncology news and interviews. We have some more exciting panels like this planned for the next few months. Thank you again, and I hope everybody has a great day.

About the Panelists

Samuel Kareff, MD, MPH, is a Medical Oncologist and the Chief Hematology/Oncology Fellow at the University of Miami's Sylvester Comprehensive Cancer Center and Jackson Memorial Hospital in Florida. He has special research interests in health advocacy, public policy, cancer prevention, and the development of cancer therapies.

Maria Badillo, MSN, RN, OCN®, CCRP, is the Research Nurse Manager in the Mantle Cell Lymphoma/Myeloma Department at The University of Texas MD Anderson Cancer Center. As a clinical trial manager, she develops research strategies and programs, manages protocol design and implementation, and coordinates patient participation in phase 1, 2, and 3 clinical trials of novel therapeutics for patients with hematologic malignancies.

Matthew Hadfield, DO, is a Hematology/Oncology Fellow at Brown University/Legoretta Cancer Center in Providence, Rhode Island. His research focuses on melanoma and early-phase clinical trials. His main areas of interest include early-phase drug development, novel immunotherapeutic combinations to overcome therapeutic resistance, and predictive biomarkers for immunotherapy toxicities.

Alankrita Taneja, MD, is a Hematology/Oncology Fellow at Roswell Park Comprehensive Cancer Center in Buffalo, New York. She is interested in multiple myeloma and cellular therapies and is passionate about humanism and equitable care.

For More Information

Ostmeyer J, Park JY, von Itzstein MS, et al (2023). T-cell tolerant fraction as a predictor of immune-related adverse events. J Immunother Cancer, 11:e006437. DOI:10.1136/jitc-2022-006437

Kumar SK, Alsina M, Laplant B, et al (2022). Fixed duration therapy with daratumumab, carfilzomib, lenalidomide and dexamethasone for high risk smoldering multiple myeloma – results of the ASCENT trial. Blood, 140(supp_1):1830-1832. DOI:10.1182/blood-2022-168930

Shah U (2023). A whole foods plant-based weight loss intervention improves metabolic and immune biomarkers in MGUS/SMM patients as well as progression trajectory in a subset – the NUTRIVENTION trial. Presented at: 2023 International Myeloma Society Annual Meeting. Abstract P-483.

Transcript edited for clarity. Any views expressed above are the speakers' own and do not necessarily reflect those of Oncology Data Advisor.