Barriers, Practices, and the Road Ahead for CAR T-Cell Therapy in the Community Setting: A Q&A With Michael Byrne, DO

AJMC: Are you seeing different regional perspectives in CAR T-cell therapy adoption in the community setting? Where might adoption be weaker, and why?

Michael Byrne, DO: We are seeing differences across practices. Some are very enthusiastic; some less so. The level of enthusiasm is driven by how close the nearest authorized treatment center is, the number of potential patients available to support the service line, and the resources a practice has to dedicate to it. Starting a program requires a physician champion—or a couple of champions—willing to lead the charge, and those resources tend to exist in larger practices. Adoption tends to be weaker in smaller practices and in those that are geographically closer to existing authorized treatment centers. Practice size matters because this is a complicated service line. You need people in the revenue cycle—what we call the back office—to work through single-case agreements, and you need a hospital partner that is sufficiently sophisticated to handle a fairly high-complexity patient population.

AJMC: What are the most significant barriers community oncology practices face when considering CAR T-cell therapy adoption—clinical, operational, and financial?

Michael Byrne, DO: Clinically, CAR T is a different service. These patients are managed more like transplant patients than chemotherapy patients: Care is highly protocolized and SOP [standard operating procedure] driven, which is unique to community oncology. You need people who can develop those processes and shift the way the practice thinks about caring for oncology patients. Clinicians also need experience managing cytokine release syndrome and [immune effector cell–associated neurotoxicity syndrome]. Historically, that experience came from academic centers and hospital-based programs, but more recently it’s been gained through T-cell engagers and bispecifics, and fellows are now coming out of training with exposure to this space as well.

Operationally, you have to have a hospital partner, somewhere to send patients when they get sick, whether it’s 4 in the afternoon or 4 in the morning. That requires systems and processes in place to support these patients 24 hours a day, 7 days a week.

Financially, this is the highest-ticket item on our formulary by a wide margin, and unlike most drugs, it isn’t spread across 6 or 8 cycles. It’s administered in roughly 30 minutes. That makes it unforgiving if a patient’s insurance lapses or their benefits change. There’s a significant amount of planning required to confirm authorization, negotiate favorable single-case agreement rates, and ensure coverage is in place at the time of infusion. In our experience, it is not a particularly high-margin service line, so we have been very meticulous about spending to keep the program on solid financial ground.

AJMC: What clinical decision support or diagnostic tools would facilitate CAR T-cell therapy adoption in community oncology, both in terms of identifying patients and treating them in the community setting?

Michael Byrne, DO: On the identification side, the message that has resonated most in our practice is straightforward: If you would give a patient salvage chemotherapy—GemOx [gemcitabine and oxaliplatin], MiniCHOP (reduced-dose cyclophosphamide, hydroxydaunorubicin, oncovin, and prednisolone)—they are probably a candidate for CAR T cells. Don’t try to filter or assess candidacy on your own. Send them and let us evaluate. That approach has gained traction, and we’re now seeing significantly more second- and third-line lymphoma patients than we used to, whether for CAR T, T-cell engagers, or clinical trials. The broader message that needs to go out is that this is safer and easier than a transplant, and many patients will tell you it’s actually easier than 6 cycles of R-CHOP [rituximab plus CHOP].

In terms of treating in the community setting, 1 major advantage is continuity. When patients stay within our system, we can manage their disease, be meticulous with bridging therapy, and move them from identification to infusion in a much shorter time frame than the national average for vein-to-vein time. Everyone we have intended to treat at our program, we have been able to treat. Keeping patients in the community oncology setting increases their comfort and leads to a smoother, shorter road to treatment.

AJMC: What pain points do you anticipate or are you currently seeing around the logistics of delivering CAR T-cell therapy in the community setting, now and looking ahead?

Michael Byrne, DO: Currently, working through payer contracts and single-case agreements is a laborious process. There have been patients we were unable to treat because we were out of network or because we are not yet FACT [Foundation for the Accreditation of Cellular Therapy] accredited. Sending patients out of your center when you are in the early stages of building a program—trying to grow, pay your bills, pay your staff—is a very difficult thing to do. I hope those will not be future-state challenges.

Another current pain point is product toxicity. Some products in the CD19 space are more toxic than others and rely heavily on having an adjacent inpatient hospital. For smaller or more rural clinics without nearby hospitals, or with low-acuity hospitals that can’t support the service line, that is a meaningful barrier. But I anticipate that as products become safer and easier to administer, the need for an adjacent hospital will diminish.

Looking ahead, my hope is for widespread adoption that is not governed by payer networks or accreditation status alone. The availability of a health system should not determine whether a practice can participate, though it may continue to influence which products a site can offer and which patients are best served in that setting vs a higher-acuity environment. Those are the kinds of nuanced discussions I hope we’ll be having a few years from now.

AJMC: What is the role of accreditation, such as FACT, in the delivery of CAR T-cell therapy in community oncology, and do you believe it is necessary for all community sites?

Michael Byrne, DO: This is a genuinely controversial topic right now. At Tennessee Oncology, we submitted our compliance application a few weeks ago and are pending our on-site inspection, so we are moving forward with FACT accreditation and anticipate being accredited this year. The process has required a significant amount of work from myself and our team, and I’ll say candidly that we identified and fixed real things as a result of getting our house in order. We are a better program because of the accreditation process.

That said, the harder and more resource-intensive the accreditation process is, the more difficult it will be for some practices to get there. Tennessee Oncology is a large, well-resourced practice—one of the larger community oncology practices in the country—and just because we can do it doesn’t mean every practice can. If payers or other bodies require accreditation, that creates a bar, and the rigor of where that bar is placed will determine how many sites can ultimately deliver this therapy.

I don’t think accreditation should be a blanket requirement for all community sites. I think every community oncology site should evaluate whether they are able to pursue it and determine which accreditations, if any, are appropriate for their practice and their patient population.

AJMC: What are some best practices that could jumpstart activation and implementation of CAR T-cell therapy in community oncology?

Michael Byrne, DO: There is a lot of momentum right now, with many practices in the early stages of standing up programs across our network and others. As a field, we are all building experience simultaneously, and we should learn from each other. The manufacturers have done a good job providing resources, and I would encourage sites to lean on those resources, but equally important is socializing, collaborating, and learning from what others have done and what hasn’t worked.

Many practices have playbooks and shared documents they can circulate. Colleagues often have SOPs from prior roles or institutions that can serve as useful references. Borrowing those materials isn’t a substitute for thinking critically about your own processes and the specific care your patients will receive at your center, but it gives you a starting point and a sense of how others have approached the same challenges.

In terms of key stakeholders, I’d highlight 3: the manufacturers, an apheresis provider, and a hospital partner. For manufacturers, sites should think carefully about which products to onboard and in what order: Prioritize the ones that are easiest to work with, actively seeking new sites, and have the smoothest startup timelines. Get an early win or two. For apheresis, many community practices are relying on third-party providers—hospitals, blood banks, dialysis clinics that are entering this space—rather than standing up their own programs. And finally, you need a hospital partner that is familiar with CAR T, has a good working relationship with your practice, and can develop protocols for managing these patients if they present to the [emergency department] or [intensive care unit].

AJMC: In the next 5 years, how do you see the role of CAR T-cell therapy evolving in the outpatient setting?

Michael Byrne, DO: I think in 5 years, the majority of patients will receive CAR T in the outpatient setting, driven either by an inevitable shift in practice patterns, by the products becoming safer, or both. I also expect that the patient population will diversify significantly. These won’t only be hematologic malignancy patients. We’re going to see solid tumor patients receiving cellular therapies, and there is a great deal of energy around autoimmune indications. Five years from now, I expect we’ll see a meaningful diversification of both the patients being treated and the settings in which they receive care.

I would also add that CAR T is moving into earlier and earlier lines of therapy. Many patients already find it easier to receive a CAR T-cell infusion than to go through multiple cycles of chemotherapy. As these therapies move into earlier lines, become safer, and patient preferences become a more prominent part of the conversation, people are going to ask why they should undergo a longer, more toxic regimen when a shorter, less burdensome option exists. We will need to tune our ears to that.

On the autoimmune front specifically, community oncology practices will need to determine on their own whether that is a space they want to enter. In hospital-based programs, rheumatologists and oncologists work within the same administrative structure, making collaboration more straightforward. In the community, there’s no shared administration to drive that coordination. Practices that engage will expand access; those that don’t may create the same access gaps we see today in oncology, just for a different patient population.