Procedure-wise, we collect the patient’s T cells via apheresis, which takes about six hours. Then we wait 14–28 days for the product to transform them into CAR-T cells. During this time, the patient [receives] three days of chemotherapy for preconditioning [lymphodepletion] and two days of rest, and then the CAR-T cells are reinfused. We’re even doing this as an outpatient procedure for some, which is allowing us to treat more patients.
Why is lymphodepletion with chemotherapy necessary?
MF: Lymphodepletion is needed to allow for CAR-T cell expansion. The point is to create immunologic space. We just built the patient a Ferrari. But if they’re in rush hour, it doesn’t matter if they’re driving a Pinto or a Ferrari—they aren’t going anywhere. Lymphodepletion opens up the highway so the brand-new Ferrari can take off and go.
What about complications?
MF: The number one cause of non-relapse mortality in most patients is infection. That’s because oncology and rheumatology patients don’t have normal functional immune systems to begin with. Early infections are largely bacterial, with later infections driven by viral pathogens. So in the first 30 days, we’re trying to mitigate risk, maintain appropriate blood counts and monitor for cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome.
Do rheumatology patients behave differently than oncology patients after receiving CAR-T cells?
MF: Interestingly, in patients with ARDs, we don’t see the same degree of prolonged B cell aplasia. Their B cells have the potential to reconstitute, but as a much more naive B cell population that doesn’t have as much autoreactivity.
How far off do you think we are from CAR-T cell therapy being available to patients with ARDs?
MF: Three to four years.
What are the limitations of implementing CAR-T cell therapy on a larger scale for patients with ARDs?
MF: It’s cumbersome to manufacture the individual products, and capacity to make enough would be a challenge. Cost is also an issue, with the product being about $500,000, and if you add the hospital stay about $1 million.
Do you think there could be a day when CAR-T cell therapy becomes standard of care as curative therapy for ARDs?
MF: As we make cell therapy safer and better understand what we’re doing, it could be. It really comes down to risks and benefits. We started cell therapy trials in end-stage oncology patients with relapsed/refractory disease. Now, we are using it in second-line patients, and current trials are looking at it as first-line therapy. I think there are certain high-risk patients with ARDs where it could make sense as first-line. We are working on therapies to prevent side effects and complications. If we can develop the right strategy and decrease the likelihood of toxicity, it could open the door for more patients.
