Exploring the IO Interface: Bridging Knowledge Gaps in Immunotoxicity Management

As innovations in cancer immunotherapy reshape treatment paradigms in oncology, the question of how to effectively recognize, prevent, and manage immune-related toxicities has become increasingly urgent. Additionally, emerging research and technologies are amplifying the role of precision medicine in personalizing care and identifying which patients are most vulnerable to immune-related adverse events (IRAEs).

At the 2025 North American Neuroendocrine Tumor Society (NANETS) Multidisciplinary NET Medical Symposium, Alexa S. Meara, MD, explored the interface of oncology and rheumatology in immunotoxicity management in her presentation titled, “Current vs Ideal Management of IO [immuno-oncology] Toxicities: Rheumatologist Perspective.”¹

In an interview with Targeted Oncology, Meara, a clinical associate professor of internal medicine and rheumatologist at The Ohio State University Wexner Medical Center, highlighted opportunities for education and cross-collaboration between specialties, emphasizing a precision medicine approach that not only targets the tumor but also considers the patient as a whole.

Targeted Oncology: What educational resources are available to prepare community oncologists to recognize and initiate management protocols for highly specialized immunotoxicity events?

Alexa S. Meara, MD: That is something I think is actively evolving.… In the bigger picture of the national and the international world, the Alliance for Support and Prevention of Immune-Related Adverse Events [ASPIRE], which I helped found with Carrie Reynolds [MD, Pediatrix/Obstetrix Medical Group of Colorado] and Pauline Funchain [MD, Stanford Medicine], has a “Community of Practice” [web] page, and that is what we're trying to curate––information for community oncologists [to learn about managing IRAEs]. The idea of the 501(c)(3) nonprofit [organization] that I founded in this space, the Foundation for Autoimmune Cancer Support at AutoimmuneCancer.org, is to put curated information [for community oncologists] to have better knowledge [of these events].

There's also a company called Citrus Oncology that is there for second opinions or help with IRAEs, knowing that there's an access issue. There are useful videos in the American College of Rheumatology. They [also have] what's called Rheum2Learn. It’s for internal medicine residents, but some of them are on arthritis and various drugs. So, if your question is about how [to] use [a drug], there are some opportunities there. But again, that's another click.

For internists, residents, [and advanced practice providers], as well as community oncologists, what we're trying to figure out is, what is the minimum [amount] of information that we can give to busy clinicians? How do you take care of the patient in front of you at that moment in time? Those of us in academics have been using the MedNet a lot, which is nice because you can ask a question [and] all the academics can answer, but it may not be an immediate answer within 24 hours. A lot of academic institutions are trying to figure out how to integrate rheumatology and other subspecialties into oncology or how to have IRAE or [immuno-oncology] talks in patient service. I think there [are] a lot of works in the fire, because that question is what everyone wants.

Through the ASPIRE mechanism, we're trying to figure out a list of articles besides, obviously, the American Society of Clinical Oncology guidelines [and] National Comprehensive Cancer Network guidelines. I'm not trying to minimize those work[s], [but] when you're busy and have to take care of a patient, you don't want to Google and PubMed 7000 articles, figure out what drug to use, [and] how to use this drug. So those are things we're actively doing.

I would say, stay tuned. [That] question is timely. We are trying to curate that. There is no 1 great resource right now.… I think there [are] a lot of resources to come, but my hope would be we can have this conversation in about 6 months, and then I can provide a nice little packet of information. It’s all over the place, and that’s the biggest problem. How do we herd all the cats, all the different subspecialties, to make this easier for oncologists, particularly community oncologists, to take care of these patients?

What predictive biomarkers are being investigated to stratify patients who are most at risk for severe or prolonged IRAEs?

I think this question is almost cancer agnostic because I think all oncologists are asking this question. In rheumatology, we haven't figured out biomarkers to begin with. I think this is the hot topic in precision medicine––the question is going to [be more about] immunophenotyp[ing] people.

[For] example, in the world of juvenile idiopathic arthritis, [first-line treatments of] children with arthritis are based on family history. If they don't have psoriasis, but their parents have psoriasis, they're going to be treated like psoriatic arthritis because of the genetics and the presumed response. That doesn't mean you don't pivot or you don’t change it if you’re wrong. We need to take a very good history of patients and [ask], “What box do they fit in?” If they have histories of psoriasis, uveitis, or [disease in] different places, they may have much more of an immunophenotype, which is going to then be a better biomarker to certain drugs that fit for drugs that treat psoriatic arthritis––so blocking interleukin [IL]-23 or IL-17––and those could be a lot better treatments, either when they develop an IRAE or if they have preexisting autoimmune [conditions]; that’s what we give as prophylaxis.

I think it's better to think about these as immunophenotypes in that we used to think about patients like, they had a life, then got cancer, we treat[ed] them with cancer, and then they either lived or didn't. I think the whole world of immunotherapy and cellular therapy is going to change that, because now [the patient’s] whole world matters beforehand. Who they were, what diseases they had, what those genetics are, and what drugs there are now are going to matter to what we're going to treat them for and their response. Then we want to maximize the immunotherapy and minimize the toxicity––what drugs can we combine, almost like a 1 plus 1 equals 3.

The problem is, if we don't focus the immune system, an unfocused immune system––those cytokine storms––has all these autoimmune [adverse] effects. It’s like a tired toddler. They are angry, they are spinning, and they wait until you fall down. And the only thing you can do is give them steroids, because you want to hammer the immune system down.

What we need to get to is this immunophenotyping. When you upregulate the immune system with immunotherapy, it's more focused to attack the cancer, and then whatever their pathway of least resistance is for inflammation, whether it's in the heart, cardiovascular risk factors, arrhythmias, heart attacks, arthritis, psoriasis, or rashes. We have a whole list of drugs in the nononcology space that can be used well and safely with these drugs, and that's what we're trying to marry in this space of rheumatology-oncology.

In short, the answer is, there are no great biomarkers at all. I think oncology is a huge opportunity to partner with rheumatology. Are autoantibodies useful? How do we risk stratify? And I think the question is more than just biomarkers. I think it's more about how...we create more precision medicine to see and treat the patient in front of us, because everyone's a little different. These “boxes” now in this space are not the same, so 1 lab may not mean the same thing for 1 person. It's like if anyone has knee pain and osteoarthritis and gets an x-ray. Some x-rays look terrible, and your doctor looks at you and goes, “How are you walking?” And some x-rays, you get profound pain, and your x-ray looks fine. [Because] we don't understand those mechanisms of biomarkers yet and how to interpret them, I think it's going to be a bit more of a gestalt and a composite score until we get better at those markers.

REFERENCE

1. Meara A. Current vs ideal management of IO toxicities: rheumatologist perspective. Presented at: 2025 NANETS Multidisciplinary NET Medical Symposium; October 23-25, 2025; Austin, TX.