Bridging the Gap Between Oncology and Rheumatology

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June is Cancer Immunotherapy Month, and Targeted Oncology is highlighting stories on this developing field of research.

While immunotherapy has become a mainstay of cancer treatment, it is not without its drawbacks. Immunotherapy works by stimulating the immune system to attack cancer cells. However, it can also disrupt the immune system and lead to autoimmune diseases that can last for weeks or years. Alexa Simon Meara, MD, emphasized the importance of a rheumatology approach to immunotherapy treatment to cancer to deal with some of these issues.

Meara, an associate professor in the Division of Oncology at The Ohio State University Wexner Medical Center James Cancer Center, noted there is not a lot of research on how to treat these new diseases, but rheumatologists can help care for patients who experience them.

“My goal is to work with the oncologist. If they want to continue the immunotherapy, I can figure out how to do that. It is just about that partnership and how to best do that,” Meara said in an interview with Targeted OncologyTM. “I do think that the unfortunate silos of industry, medicine, academics, and finances have created this problem to be astronomically harder to fix than it should be.”

In the interview, Meara discussed how rheumatology and oncology can work together to improve outcomes for patients undergoing immunotherapy treatment.

Alexa Meara, MD

Targeted Oncology: What is the importance of including a rheumatology approach to immunotherapy treatment for cancer?

Meara: Immunotherapy has changed the landscape to make cancer more [of a] chronic disease, which is great, right? It disrupts the immune system in specific targeted checkpoints to upregulate the immune system to allow T cells to attack the cancer. But when you dysregulate the immune system, you open the door to autoimmune disease.

This is an important point of what we don't understand about autoimmune diseases in general. In lupus, rheumatoid arthritis, we do not know what causes those diseases to begin with. What we tell people is it is the right genetic host with the right environmental stimulus. That is why we ask about family histories and different things. But not everyone in the same family will have the same autoimmune disease.

So now that a patient has cancer, they already have an up and up immune system, because there is a foreign body they are trying to attack. Now we are trying to heighten that immune system to attack the cancer by turning off certain regulatory checkpoints, getting the immune system to rise. Therefore, you now have an open door to an unregulated immune system. So, what is that second hit? What is that environmental stimulus? We have no idea. But then that opens the door to a wide variety of autoimmune diseases that can happen in any organ at any time.

I think this idea that somehow, we can predict [autoimmune diseases], we have not been able to do that in rheumatology ever, and we have a whole specialty related to that. Oncologists are so good at trying to be predictive, and it is interesting to take a black-and-white world, and we are marrying it with a very gray world. It is like the yin and the yang of it; it is still figuring itself out in that kind of sense. It is like we are still trying to feel each other out the beginning of the marriage; we are trying to figure out how to load a dishwasher without fighting.

I think even immune-related adverse effects or the toxicity of immunotherapy is a wrong name. We have already had them for 15 years, and we have had all this research with this, so I do not want to change the name, but it is not an event. It is actually a new disease, a new sequela. Some are one and done. Some are one and done over a year. Some happen a year to 2 years after [the patient has] already had the drug. Some may be chronic, and we are with the patient for the rest of their life. Because we do not quite understand how to predict them, we are not quite there on diagnosis because it is a brand-new disease. We do not quite understand pathophysiology.

We do not have a lot of clinical trials, and medicine already is so siloed in the sense of who should be taking care of these patients. I would argue, and I know my bias group as a rheumatologist, that oncologists are good at treating cancer. There is a reason why there is a subspecialist in treating autoimmune disease. This is not a turf war. This is an opportunity to take care of [patients with] cancer and a new thinking about survivorship.

But that is a huge paradigm shift. We are so siloed. This pathway that academia and medicine has become does not fit now with where public health is going. There are massive changes in where medicine is going to need to be, and I think this is one way to think about this.

For oncologists, [we have] surgical oncologists, radiation oncologists, so do we need now rheum-oncologists? Cardio-oncology already exists, endo-oncology, pulmonary oncology. Do we need new subspecialties to be all together and have these multidisciplinary clinics? My argument would be 1000% yes, because we are doing it, but we are just piecemealing it together now rather than doing it more seamlessly.

But this is a huge change and an exciting change. This is an opportunity. We went from survivorship of thinking about 3, 6, 12 months and now 5, 10, 20 years. That matters. And now if you have inflammatory arthritis, which means you cannot hold a coffee cup, or walk up and down stairs, if that is going to last for 2 years, it is very different than if it lasts for 3 weeks. How we treat that, and how we treat those using drugs we already have for rheumatology, all these targeted therapies to ensure the safety of those drugs [and that they do not] mess with the antitumor effect of the other drugs is going to be vital.

I think industry is equally to blame and equally to have an opportunity. Because before [chimeric antigen receptor (CAR) T-cell therapy] existed, rheumatology and oncology never talked. If you walked into big pharma, they wouldn't know who worked in another division. All of a sudden, even industry and the FDA are starting to look at things differently.

[I think we need to] to move medicine to more of a public health need and true precision medicine where patient truly is in the center and the specialties run around the patient, rather than they run around their own division. I actually think the only person that could probably do this would be an oncologist, because they have the lobby, they have the money, they have the capital, and they have the patience to actually move this forward. I think oncology should take this as a big win, and they do not have to do it all. We can be there to do it together and partner together. I think that is why my clinic has been so successful. I sit in oncology, and we are doing this together, and creating a system for patients to move to try and keep them out of the hospital to try and manage their [adverse] effects to improve their quality of life to ensure that the cancer is still the number 1 focus, but with a close second being quality of life.

How is the interaction between oncology and rheumatology built? When are you brought into the cancer treatment timeline?

As a physician, I had a reputation. I have always been kind of the zebra doctor; I took care of things that no one quite understood. When immunotherapy started and [oncologists] started seeing the [adverse] effects, they did not know who else to ask. They started to ask me, and then this became a very public health issue. Everyone started to pay attention, and more and more articles came out. Due to the silos, it seemed easier if I can just sit in oncology. [Patients can] refer themselves to me. They can ask the oncologist, or [the oncologist can refer the patient].

It is a collaborative thinking process if the patients are complaining about certain [adverse] effects. Oncology, in the past, has been trained for chemotherapy [adverse] effects, which are incredibly predictable. There are obviously subtleties involved in cancers and targeted therapies, but they [are not] a vague, smoldering autoimmune disease that is difficult to diagnose, that takes trial and error, and has to [consider] various organ systems all the time. That's what I do. It is a relapsing, remitting chronic disease with multisystem organs, and you basically pivot all the time. This drug works, then this one stops working, then you pivot and you start again, and then insurance gets involved. It is just this constant cycle. But that is what I am trained to do. That is not what oncologists are trained to do. That doesn't mean they cannot do it. Every physician that is an MD could probably deliver babies, but that does not mean they should, right?

I also recognize an access problem. There are not enough rheumatologists in the country for regular rheumatology diseases, let alone now with cancer stuff. I think it's about how we create better systems. Part of what I do, and what I'm working with in our national is we created an immune-related adverse effects research consortium, and we named our research consortium Aspire, and we have a patient advocacy group called Stories, and we're working on trying to build that. It can marry the American College of Rheumatology plus the [American Society of Clinical Oncology (ASCO)] guidelines, so there is a home that shows it right there together vs you trying to Google everything. Yes, it is all out there on the internet, but that is overwhelming. If you are a community oncologist, and you are trying to do this by yourself, and you are seeing 25, 30 patients a day, and they have all these autoimmune [adverse effects], where do you go? Who do you call? How do you do that? How can we make things simpler, so that patients can get the treatments they need? How do we have the evidence for that? How do we find these studies? All the societies, all the people that need to be involved, the stakeholders buy into this process together. We are trying to do that, but it is a little bit of herding cats and trying to get everyone on the same page. But it has been universally so far well accepted. And what I think everyone has noticed is academic medicine is not great at infrastructure, so that takes time.

This has been a challenge to integrate in an academic center and a comprehensive care center where the resources are already somewhat consolidated. What would be your steps for a community oncologist who maybe doesn't have that network built in?

Anyone can email me at any time. I am happy to help. I think post-COVID, every place is trying to think about how to do things telehealth-wise. I have a colleague that is trying to work on a second opinion group called Citrus Oncology. The idea is could you have access nationally. As a physician, why am I only limited to Ohio? How do we get expertise out? I think this is a problem that everyone is trying to figure out how to solve, and we have not had quite the answer yet.

I think the more that you ask the questions, the more it will come. Unfortunately, in the United States in the healthcare system, sweat equity is how this is going to start. Then, having patients’ voices be strong and loud to advocate and tell your oncologist that you need help. It is not trying to shame the oncologist and tell them they do not know what they are doing. It is just going, how do we make your life better as an oncologist, so you can focus on the treatment, and then I can do this over on this side? I think it is quite helpful.

I would say for community oncologists, if you are not in or near Ohio, there are many of me out there in the US. A lot of us rheumatologists are very interested in this field. Find your local academic center, email the division chief, and be like, “I need a point person.” I can tell you they probably be so excited to have a point person to get patients in and create a streamlined process. But it is going to create a little bit of legwork, and that I do not know how to fix.

I have also heard that sometimes that we do not know who the head chef is. So, the oncologist will email a subspecialist, but then they will kind of punt them back. But I think it is because that expectation of who is taking care of what has not been clear. Everyone in OSU Oncology knows when it comes to the adverse effects, I am head chef. I get to run this. They are clear with that, and I keep them in the loop. I am not doing things without them. I am doing evidence-based things and having conversations.

That can be hard if you are a community practice and your local rheumatologist is 5 hours away. How do you create that meeting? I think that is another opportunity for industry. Because industry knows who all the private practices are and can maybe make some connections for people.