Rare Disease Day With Thomas Abrams, MD; Maria Badillo, MSN, RN, OCN®, CCRP; and Ulka Vaishampayan, MD

Oncology Data Advisor: Hi everybody. Welcome to Oncology Data Advisor. Today, we're holding a panel discussion with our Editorial Board in honor of Rare Disease Day. I'm joined by our Editor-in-Chief, Dr. Thomas Abrams, who is an Assistant Professor of Medicine at Harvard Medical School and Institute Physician at Dana-Farber Cancer Institute, and he'll be discussing rare gastrointestinal cancers. Dr. Abrams, thanks for joining today.

Thomas Abrams, MD: Oh, it's my pleasure. This is really exciting. Thanks for having me.

Oncology Data Advisor: Of course. We also have Maria Badillo, who is the Research Nurse Manager in the Department of Lymphoma/Myeloma at MD Anderson Cancer Center, and she'll be discussing nursing management of mantle cell lymphoma. Maria, thank you for joining as well.

Maria Badillo, MSN, RN, OCN^®, CCRP: Thank you, Keira, for the invitation. Glad to be here.

Oncology Data Advisor: To start off, Dr. Abrams, would you like to tell us a little bit about the rare gastrointestinal (GI) cancers that you see in your practice?

Dr. Abrams: Sure. I mean, we have so many GI cancers in general; there's such a variety. There's a number that are actually quite uncommon. But I think the two that really are great for this panel discussion are cholangiocarcinoma and anal cancer. I wouldn't call them necessarily rare, but they're uncommon—particularly when you think about them in comparison to, say, colon cancer and pancreatic cancer, which are much, much more common. Cholangiocarcinoma affects maybe 10,000 patients a year in the United States, maybe a little more, maybe a little less. It's hard to pinpoint the number, but it's a small number in general.

There has been enormous research into molecular changes that have ushered in whole new types of treatments that are directed towards specific mutations. We also have a new option for the first-line treatment of metastatic cholangiocarcinoma that includes immunotherapy. I want to talk a little bit about what we can find in intrahepatic cholangiocarcinomas that can change the treatment.

Anal squamous cell carcinoma is a pretty uncommon cancer. The incidence is only about 5,000 to 6,000 a year, although the incidence is rising. It's a human papillomavirus (HPV)–related cancer, and it also has great responses to immunotherapy. It's an interesting cancer from a therapeutic standpoint, as well. Those are the two that I'd like to talk about today.

We'll talk about cholangiocarcinoma first. Cholangiocarcinoma is a disease that arises within the liver, typically in the bile ducts. We're speaking specifically about intrahepatic cholangiocarcinoma. These are the cholangiocarcinomas that arise within the bile ducts, within the liver. It turns out that about 35% of them will have an actionable mutation or molecular abnormality that allows them to be targeted by certain drugs.

The things that we find most often are isocitrate dehydrogenase (IDH)1 mutations, IDH2 mutations, fibroblast growth factor receptor (FGFR)2 fusions, and certain FGFR mutations as well. The FGFR2 fusions have a number of drugs that are now approved in the second line. Most recently, the covalent FGFR2 inhibitor called futibatinib was approved, and that seems to be the best in class. Cholangiocarcinoma is the only disease in which futibatinib is approved, so it's a very interesting drug. Then for the first-line treatment of all biliary tract cancers, we have a new regimen based on a phase 3 study that combines chemotherapy consisting of gemcitabine and cisplatin with a drug called durvalumab, which is an immunotherapy, a programmed death ligand 1 (PD-L1) inhibitor.

So, we have this raft of new treatments that have really changed the game and made the disease a lot more manageable. It's still a very, very difficult disease to treat, and I don't want to give the impression that it's now something that we're doing great with. But patients are living longer, and there's a lot more optimism. There's also the IDH1 inhibitor, ivosidenib, which is also approved after failure of gemcitabine-based therapy. It's another targeted agent with very few side effects that can really improve our patients' outcomes. It's an exciting area, and we call cholangiocarcinoma "the GI lung cancer" because there are so many molecular targets that you can go for.

Anal squamous cell carcinoma is an uncommon disease of the anal canal, and it is related about 95% of the time to the presence of human papillomavirus. Typically, patients are going to present with some bleeding, maybe a little bit of pain. When it's localized, we treat it, interestingly enough, with just chemotherapy and radiation, and we get a cure rate of about 65% to 70% with just that—no surgery. If there's residual disease at six months after completion of the chemotherapy and radiation, then a salvage surgery is indicated. That's an abdominal peroneal resection (APR), where the entire anus and rectum have to be removed. The patient obviously would then need to have a permanent colostomy, which is not what we're hoping for when we treat this illness.

When it's metastatic and/or recurrent, then we can treat with chemotherapy and also immunotherapy, many times with good results. It is a disease in which there are increasing therapeutic avenues that we can go down, particularly because we know that in other HPV-related cancers, immunotherapies tend to be very effective, and this is no different. It's an interesting cadre of diseases in the GI world. There are other rare diseases that we don't see that often, but those are the two that I think are most interesting.

Oncology Data Advisor: What are you most looking forward to for both of those within the next five years or so, as far as research?

Dr. Abrams: We saw microsatellite instability (MSI)–high rectal cancer that you can treat an MSI-high local rectal cancer with just dostarlimab, which is an immune therapy, and get basically a 100% complete response rate, obviating the need for surgery and radiation and all these things that we do in rectal cancer. I think a similar study needs to be done in anal cancer. Now, I don't know that we'll get the same degree of response to immunotherapy, but I think it's worth looking at. That's a study that I'm excited to participate in and I think could really, really elevate how we treat this disease and take away a lot of the morbidity that is associated with chemotherapy and radiation, while simultaneously getting an even higher cure rate. I'm very excited about that.

Then in cholangiocarcinoma, as we plumb the depths of the molecular targets, we're going to find that more and more patients are going to have targetable molecular abnormalities, and we're going to see more and more drugs come online that are going to really improve the outcomes for these patients. Specifically, we'll be taking these drugs that are now approved in the second line and moving them to the first line, combining them with chemotherapy and seeing what happens. I think that's a very exciting way to treat patients. These trials are coming online, and I'm very excited to enroll to them. This is how the field is changing, and it's a good time to be treating these illnesses.

Oncology Data Advisor: Awesome, that's very exciting. Thank you so much for explaining all of that.

All right, Maria, we can transition over to you. Would you like to start off by telling us a little bit about what you do in your role at MD Anderson, and then we can talk about what you see with the mantle cell lymphoma (MCL) patients that you treat?

Ms. Badillo: Hi Keira, thank you for the opportunity. I am a Research Nurse Manager at our institution. I'm happy to say that today is actually my 15-year work anniversary. I've been working with MCL for that long.

Just a brief background about mantle cell lymphoma: this is a rare type of lymphoma, making up 6% to 7% of all non-Hodgkin lymphomas. The median age at diagnosis is usually about 70 years old, predominantly male. Typically, our patients have generalized lymphadenopathy. Some patients often have extensive involvement in their bone marrow, blood, and GI tract, particularly the colon. And 40% of patients have B symptoms, which are fever, night sweats, and weight loss.

Mantle cell lymphoma is still an uncurable disease. Over the 15 years that I've worked with our patients, there are six drugs that have been approved by the FDA, which are lenalidomide/bortezomib; the Bruton tyrosine kinase (BTK) inhibitors ibrutinib, acalabrutinib, zanubrutinib, and the most recent approval of pirtobrutinib; then in July 2020, the FDA granted an accelerated approval to brexucabtagene autoleucel, which is the CD19-directed chimeric antigen receptor (CAR) T-cell therapy.

Oncology Data Advisor: Great, and congratulations on your 15-year anniversary.

Ms. Badillo: Thank you.

Dr. Abrams: Yes, that is great. So, what is the role of nursing in terms of oral drug compliance for MCL patients?

Ms. Badillo: As I mentioned earlier, most of the approved drugs for MCL are oral, so compliance is important, especially for our patients who are taking these drugs at home. Over the past couple of decades, oral chemotherapy drugs have forged a new therapeutic option in providing cancer patients with a more manageable, less invasive alternative to standard intravenous (IV) chemotherapy administration. Unlike traditional infusion oncology, where the doctors, nurses, and pharmacists directly oversee the process, oral chemotherapy requires the patients themselves to correctly administer the drug.

As nurses, it is very important that we do our due diligence in terms of educating our patients. With oral chemotherapy, the process is no longer under our direct control. When the patients are taking the drug at home, we never really know if they are taking it correctly. Nonadherence can lead to disease progression, additional physician visits, longer hospital stays, and increased mortality. Medication adherence involves a combined effort and understanding between health care providers and patients in the degree of conformity in regard to day-to-day treatment, dosing and frequency, duration of therapy, and discontinuation. The patient's role in medication administration is significantly crucial when adherence to treatment regimens depends on proper self-management.

Dr. Abrams: That's really very interesting. There's a lot to manage there. And now in the post-COVID era, I think that would probably even increase the amount that you have to manage. Tell me how you do that.

Ms. Badillo: That's correct. During COVID, most of our patients, of course, were scared to fly back to Houston. Most of our patients come from all over United States, and some are outside United States. Nurses really have a very big role in education regarding oral adherence and managing adverse events. Some of our patients are scared to fly, so we ask them to do local labs. Then they have to send it to us to check to make sure that it's within normal limits and they can proceed to the next cycle.

Dr. Abrams: Do you find that the lines of communication can get a little bit difficult to manage, or do you have a way to streamline that process?

Ms. Badillo: In the beginning, it was very hard. Like I said, most of our patients are elderly, so they're not used to a lot of remote visits and calling. But now they're very technologically savvy. They're very advanced now, and they can even text us back if they need us.

Dr. Abrams: Oh, that's terrific. That's great. And it looks like we have Dr. Vaishampayan on the line.

Oncology Data Advisor: Hi Dr. Vaishampayan, hope you're doing well. Would you like to introduce yourself and tell us about what you do in your role?

Ulka Vaishampayan, MD: Hi everyone, my name is Ulka Vaishampayan. I'm a Medical Oncologist at the University of Michigan in Ann Arbor. My focus and expertise and both clinical practice and clinical trials with development of novel agents. My focus of clinical practice is genitourinary tumors.

Because of that, I have a whole slew of rare diseases that I deal with all the time, the main one being kidney cancer. Within kidney cancer, the non–clear cell histologies are considered rare. Then there is penile cancer as well as testicular cancer, which is not all that common, but is definitely a very important problem that needs to be addressed.

Oncology Data Advisor: What are some of the biggest challenges that you see when you're treating these diseases, since they're so rare? And then also, what's some of the exciting research that you've seen lately in them?

Dr. Vaishampayan: Most of the time, our biggest priority is to practice evidence-based medicine. Unfortunately, in rare diseases, there are not as many large trials that will guide us and give us adequate information to make those treatment decisions. That, I think, is the biggest challenge in these rare diseases. Obviously, if we can find a very crucial genetic abnormality or a mutation, that will give us an inkling as to treatment. For example, the TSC1 mutation predicts for a huge sensitivity to mammalian target of rapamycin (mTOR) inhibitors in some of the chromophobe and non–clear cell histologies within kidney cancer.

We are making inroads into identifying some of the unique features of each of these tumors that are allowing us to personalize the therapy. But clearly, a number of these patients have no exact targets identified, so we are treating them from studies and extrapolating from patients with clear cell kidney cancer, which is the more common variety frequently. The other challenge, of course, is in terms of prediction of prognosis and discussion with patients about what kind of treatments to pursue and what to expect from their disease.

Dr. Abrams: How do you go about talking to a patient who has a rare form of kidney cancer, say medullary kidney cancer, and knowing what to tell them about prognosis? You mentioned that it's difficult to point to any specific phase 3 trial or really any retrospective data, so that's always a difficult position to be put in.

Dr. Vaishampayan: I think you bring up one of the most challenging histologies in rare diseases, which is medullary carcinoma. It is associated with sickle cell disease, actually. It usually affects the very young patient population and disproportionately affects African Americans because the sickle cell trait is more common in those patients. This is a very aggressive disease that very rapidly spreads and metastasizes. We frequently need to have the discussion that this is an incurable terminal malignancy, and we are still trying to find our way in which treatments really work.

We do upfront chemotherapy, which can give us responses for some time. But for the most part, almost everyone relapses or regresses even though they have an initial response. If you can do surgical removal, the disease is rarely confined to the kidney. Most of the time, we find it when it's metastatic. But if it is truly confined to the kidney, then surgical management is key for these patients. I think overall, it's a tough discussion because there isn't enough focus. Now there are some studies that are looking at specific targets in this disease and trying to develop targeted therapies, but we have a long way to go in this cancer.

Dr. Abrams: Do we know why there's this relationship with sickle cell trait, or is that sort of unknown?

Dr. Vaishampayan: I don't know that we know the exact pathophysiology, but it does appear to be that sickle cell trait is frequently associated with a lot of collecting system of the kidney as a normality. Whether that chronic irritation has anything to do with it is probably a simplistic view to say that it causes the malignancy or at least triggers something.

Dr. Abrams: I was on the inpatient service a while ago and saw a patient with this. It was just shocking because I'd seen her a couple of months prior, and then she came back on service and the deterioration was just so rapid. She ended up having a massive pulmonary embolism (PE) and dying. It was just horrible, just terrible.

Dr. Vaishampayan: It definitely stays with you, and we just need to turn that emotion around and really focus on research in this disease, because I think it is attainable. With these rare diseases, there aren't enough patients, so it's hard to get the focus on them to do specific research.

Dr. Abrams: Thank you, Ulka. That was terrific. And thank you, Maria.

Dr. Vaishampayan: Of course.

Dr. Abrams: I think this is really important to shed light on these rare diseases and know that there's research. We're trying to move the needle instead of just treating as if this were some more common disease, which is sort of what we do in a lot of these diseases. But trying to find the needle in the haystack is really the key. I think we have made inroads in a lot of these diseases.

Oncology Data Advisor: Yes, thank you all so much for sharing all of this. It was great to hear about all the new research and what to look forward to in the future.

Dr. Vaishampayan: I will just make a pitch that clinical trials are the way we make advances, so encouraging your patients to consider those as the most cutting-edge treatment, especially for rare diseases, is definitely very important.

Dr. Abrams: I 100% agree, couldn't agree more. Absolutely.

Ms. Badillo: Same here.

Oncology Data Advisor: Absolutely. Well, thank you all again and thanks to everybody for watching today.

About Dr. Abrams, Ms. Badillo, and Dr. Vaishampayan

Thomas Abrams, MD, is an Assistant Professor of Medicine at Harvard Medical School, an Institute Physician at Dana-Farber Cancer Institute, and the Director of the Liver Cancer Task Force at Harvard Cancer Center. He specializes in the treatment of patients with gastrointestinal cancers, including pancreatic, gastric, colorectal, esophageal, gallbladder, anal, and primary liver cancers. Dr. Abrams' primary research interest is the early detection of liver cancers through the discovery and application of novel biomarkers.

Maria Badillo, MSN, RN, OCN®, CCRP, is the Research Nurse Manager in the 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. Ms. Badillo has been a speaker at several conferences, including the Oncology Nursing Society Congress and the Academy of Oncology Nurse and Patient Navigators Conference. Her research focuses on the development of novel therapeutics for patients with hematologic malignancies and the management of adverse events to optimize treatment outcomes.

Ulka Vaishampayan, MD, is a Professor of Internal Medicine and the Director of the Phase 1 Program at the University of Michigan Rogel Cancer Center. She is also the Chair of the Southwest Oncology Group (SWOG) Advanced Renal Committee, a member of the National Cancer Institute (NCI) Renal Task Force, and a board member of the Michigan Society of Hematology/Oncology. Dr. Vaishampayan specializes in the treatment of genitourinary malignancies, including prostate cancer, bladder cancer, and renal cell carcinoma, and her research focuses on translational drug development.

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