Addressing the Infectious Disease Challenges in Immunocompromised Patients

Joshua A Hill, MD, FIDSA, an infectious disease specialist at Fred Hutchinson Cancer Center and the University of Washington Medical Center, is focused on improving care for immunocompromised patients who face risks from infections and are often excluded from clinical research.

“Our patient population that we treat here in Seattle at our academic medical centers and our large, complex medical systems here are getting increasingly immune compromised,” Hill said. “I think we're seeing more drugs that are available to treat a variety of different conditions, to target the immune system to treat these conditions, and also our survivorship is increasing, so we're keeping patients healthier for longer, but at the expense of sometimes having medications that are impacting immune function.”

Patients with weakened immune systems are at increased risk for infections, including viral, bacterial, and fungal infections, as well as emerging infectious diseases.

“We're seeing a lot of emerging infectious diseases as the epidemiology shifts here. So I think there's a lot of challenges as we move forward in helping to protect this vulnerable sector of society and really learning how to best support them with new medical advances like new types of vaccines, new vaccine platforms, and new therapies like cellular therapy.”

Clinical Trial Exclusion

One challenge Hill highlights is the exclusion of immunocompromised individuals from clinical trials, which limits the development of evidence-based guidelines for these high-risk patients.

“One of the problems, I would say, that we've seen over the past five to ten years—and then really, if you expand beyond the COVID era—is that these highly immunocompromised patient populations are oftentimes excluded from clinical trials, which really focus on healthier general population groups of individuals,” Hill said. “Sometimes the immune compromised patients are those that we need to study the most carefully, because they are sometimes at the most risk for the infection or worse outcomes from infectious diseases, and may respond differently to treatments and may need different types of approaches than a healthy individual.”

Building a National Clinical Trials Network

To address this issue, Hill and his colleagues are working to create a national Clinical Trials Network dedicated to immunocompromised patients. The network aims to bring together institutions, investigators, and healthcare providers to collaborate on research for this patient group.

“To try to reduce some of the barriers to implementing and conducting these clinical trials, we're working on an initiative to build a National Clinical Trials Network that includes the institutions and the investigators and the healthcare providers that really have expertise in this space,” Hill explained. “We can more readily recruit patients and come together to think about what the high priority areas are, what new types of therapies we have at our disposal, and how we can best design trials to address some of the big questions.”

Hill mentioned RSV vaccination as an example of a current issue: “Which vaccine to choose, how many to give? These are some of the problems that we need to tackle as a group.”

Supporting Community Clinicians

Hill also emphasized the importance of supporting community clinicians who care for patients after they leave specialized centers. These providers may not have experience with the complex treatments immunocompromised patients receive and may need additional guidance.

“Patients will come to an institution like the Fred Hutch or University of Washington and get some really novel, complicated therapies, like CAR T cell therapy, for instance. And then after a month, we discharge them, and we say, ‘All right, now it's back to the community providers,’” Hill said. “That's really challenging. There are not great solutions, and there aren't necessarily evidence-based guidelines out there.”

He stressed the need for institutions to develop the data and guidelines necessary to support community providers. “That's part of the work that I think we need to do... so that we can optimize antimicrobial prophylaxis, vaccine strategies, and keep these individuals healthy. And once we cure them of their underlying cancer or other condition, the last thing we want to see is someone getting sick and dying from an infectious disease.”

Hill's call to action is clear: the clinical and research community must address the gaps in care for immunocompromised patients through inclusive clinical trials, coordinated research efforts, and greater collaboration.

“We have a lot of work to do there,” Hill said. “And that's part of the problem we're trying to address.”