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May 9, 2026 — Chimeric antigen receptor T-cell therapy, or CAR T, sounds like something out of a futuristic medical drama. But for certain patients with chronic lymphocytic leukemia (CLL), it is a real option. In a recent interview with AJMC, Kerry Rogers, MD, associate professor at The Ohio State University Comprehensive Cancer Center—The James, explained what actually happens during CAR T treatment, why the experience can be more grueling than patients expect, and why the therapy works well in some cancers but not others.
Rogers admits that even she finds the concept remarkable. “Every time I think about it, it still sounds like science fiction,” she said. The science may be dazzling, but she is careful not to oversell it. CAR T is not a simple infusion. It is a personalized treatment that starts with a patient’s own immune cells, turns them into targeted killers, and then asks the patient to ride out weeks of recovery that can include serious side effects.
The first step in CAR T therapy is leukapheresis. Blood is drawn from the patient, run through a machine that separates components, and the white blood cells are collected. The rest of the blood is returned to the body. Rogers says the process is similar to what happens during a platelet donation, except the goal is to pull out T cells.
Those collected cells are then shipped to a manufacturing lab. With most approved commercial CAR T products, that means a wait that can stretch into five or six weeks. During that time, the patient’s T cells are genetically modified so they can recognize a specific marker on cancer cells.
At the lab, a viral vector is often used to insert a new receptor into the T cells. This receptor is the chimeric antigen receptor, or CAR. It allows the T cell to bind to a target on the cancer surface. In many B-cell cancers, including most cases of CLL, that target is CD19. The engineered cells are then expanded, quality checked, frozen, and shipped back to the treatment center.
There are research versions of CAR T produced on-site at specialized centers like Ohio State. Rogers notes that shortening the manufacturing time is a goal, but commercial products still usually take weeks. For patients with fast-moving disease, that window can feel agonizingly long.
Before the engineered cells can be infused, the patient needs lymphodepletion chemotherapy. This is usually a high-dose regimen containing fludarabine and cyclophosphamide. It is not easy to tolerate, but it is essential.
The chemotherapy clears out existing lymphocytes, making room in the immune system for the new CAR T cells. Without this step, the infused cells often do not expand well enough to produce a strong response. Rogers calls this part of the process necessary but unpleasant.
Once the lymphodepletion is done, the living CAR T cells are infused back into the patient. That is often when the real challenges begin.
When CAR T cells expand inside the body, they can trigger a massive immune response. The signs can look like a severe infection, with fever, low blood pressure, and rapid heart rate. This is known as cytokine release syndrome, or CRS. The cytokines involved are immune signaling molecules, and when they surge, the whole body can feel the effects.
Another CAR T-specific complication is neurotoxicity. Patients may have trouble finding words, develop confusion, or, in severe cases, experience seizures or unconsciousness. Some cases can be fatal, although experienced centers have become much better at recognizing and treating these toxicities early.
Rogers says the field has improved substantially over the years. Hospitals now have protocols for using drugs like tocilizumab, which blocks the IL-6 pathway, and steroids to quiet the immune response. Preventive strategies and tighter monitoring have reduced the risk of severe illness or death.
Even so, recovery is not quick. Blood counts can stay low for weeks after lymphodepletion. Some patients experience thinking problems that linger for months. Driving is usually off limits for a while because of seizure risk. A 24-hour caregiver is typically required, similar to the setup after a donor stem cell transplant. Patients also need to stay near the treatment center for a period of time. Some CAR T products previously required a 30-day monitoring window; some now allow 14 days.
Rogers says the biggest gap between patient expectations and clinical reality is the word “curative.” Headlines tend to describe CAR T as a cure, but the truth is more nuanced. CLL can return even after a successful response, and the treatment does not erase the need for ongoing disease monitoring.
There are also long-term consequences. Because the CAR T cells target CD19, they can also destroy healthy B cells. This can leave patients with reduced antibody protection and an increased risk of infections for months or years. Some patients need immunoglobulin replacement therapy to help keep infections away.
“People don’t realize, too, that CAR T, even when it’s done, you still need disease monitoring,” Rogers explained. “It’s not 100% curative. Your CLL could come back. It’s an ordeal to go through.”
The treatment is often described as a one-time therapy, but follow-up is not one appointment. Disease response is typically assessed around day 30 and day 90. Doctors may also measure how long the CAR T cells remain in the body and whether the cancer has found a way around the therapy, such as losing CD19 expression.
CAR T has had striking results in some blood cancers, but CLL has been a tougher setting. Rogers points to several reasons.
First, the target matters. CD19 is present on CLL cells, but if the cancer cells change and stop expressing CD19, the therapy loses its grip. Target availability is not guaranteed forever.
Second, manufacturing is not always successful. Patients with CLL often have heavily pretreated immune systems. Their T cells may be exhausted or difficult to expand in the lab. If the manufacturing process fails, a patient may not receive the therapy at all.
Third, the immune environment matters. CLL can surround itself with suppressive signals that make it harder for CAR T cells to do their job. Even when the engineered cells dock onto the cancer and become active, the surrounding tumor milieu may blunt their killing power.
That is why the same approach that can drive durable remissions in aggressive lymphoma may not perform identically in CLL. Rogers emphasizes that patient selection and center experience are critical. An established center that knows how to handle CRS, neurotoxicity, and prolonged cytopenias is not optional; it is part of the treatment itself.
There is also regulatory news that has reshaped the conversation. In March 2024, the U.S. Food and Drug Administration expanded approval of lisocabtagene maraleucel, also known as Breyanzi, to adults with relapsed or refractory CLL or small lymphocytic lymphoma who have already received at least two prior lines of therapy, including a BTK inhibitor and a BCL-2 inhibitor. That decision made CAR T a more tangible option for a subset of CLL patients, not just a research concept.
Still, eligibility is not automatic. Rogers says patients should think of CAR T as a major commitment. It requires time, physical tolerance, logistical support, and a team that can monitor and manage complications. The therapy offers real potential, but it is not a walk-in, walk-out procedure.
For now, CAR T remains one of the most sophisticated tools in oncology. It uses a patient’s own body to fight the cancer, and it works in ways that ordinary chemotherapy cannot. But Rogers is careful to keep the conversation grounded. The science may feel like science fiction, but the recovery is real. Patients need to know both sides before they decide.
With more research, faster manufacturing, and better toxicity management, CAR T is likely to become more accessible for CLL. But the core message from experts like Rogers remains the same: know the process, plan for recovery, and keep expectations aligned with reality. That combination, she says, is what separates a hopeful headline from a well-informed treatment decision.
