CAR-T Safe and Effective on an Outpatient Basis

Study of liso-cel in patients with relapsed or refractory large B-cell lymphoma points to the benefits of bringing advanced therapies closer to patients, minimizing hospitalizations

(WASHINGTON – September 30, 2024) In the largest prospective study to date examining the use of chimeric antigen receptor (CAR)-T therapy in a community setting on an outpatient basis, patients with relapsed or refractory large B-cell lymphoma (LBCL) responded well to treatment with few serious side effects, according to results published today in Blood Advances.

LBCL is a cancer affecting B lymphocytes, a type of white blood cell. It can progress rapidly and is fatal if untreated, although most forms of LBCL respond well to standard cancer medications. For those patients who do not see their cancer eradicated with standard treatments (refractory) or who see their cancer return after an initial response (relapsed), CAR-T therapy can be an effective treatment option. In CAR-T therapy, a patient’s own immune cells are removed, genetically altered, and then infused back into the body to attack and kill lymphoma cells.

Pursuing CAR-T therapy can be challenging for patients and caregivers who may have to take time off from work and find temporary accommodations far from home. CAR-T therapy comes with unique and potentially serious side effects, such as cytokine release syndrome (CRS), characterized by fever, low blood pressure, and/or low oxygen levels, and damage to the brain (neurotoxicity). Patients require close monitoring and are often hospitalized for observation after treatment and advised to stay within one hour of the hospital where they received the treatment.

According to Yuliya Linhares, MD, chief of the lymphoma service at Miami Cancer Institute and study author, one of the biggest hurdles accompanying CAR-T therapy has been patient access. “Transferring patients to a new health system can cause headaches for obtaining insurance approvals, arranging appointments, and ensuring continuity of care,” she said.

In the OUTREACH study, Dr. Linhares and her colleagues evaluated the feasibility of administering CAR-T therapy on an outpatient basis to mitigate barriers to access. The study included 82 patients with relapsed or refractory LBCL who were eligible to receive lisocabtagene maraleucel (liso-cel), one of several CAR-T cell products approved by the U.S. Food and Drug Administration, having received two or more prior lines of treatment. Liso-cel was selected based on its relatively lower risk of serious side effects.

Liso-cel is one of several CAR T-cell products approved by the U.S. Food and Drug Administration and was selected for the study based on its relatively lower risk of serious side effects. The results showed that the efficacy of the treatment was in line with previous liso-cel trials, with 80% of patients experiencing an objective response to treatment, meaning the cancer was significantly reduced or eradicated, and 54% experiencing a complete response, meaning no residual cancer was found.

“I’m very excited to see this therapy offered to a wider range of patients,” said Dr. Linhares. “Traditionally, CAR-T cells have been administered by expert teams at university-based medical centers, which of course limits access to this very-needed therapy. The longer patients have to wait for CAR-T administration, the worse the outcomes. It is important to show that this therapy can be safely given not just in university-based medical centers, but also in community medical centers, and that it can be given not only in an inpatient setting but also in an outpatient setting.”

Nearly three-quarters of the centers involved in the study had not previously treated patients with CAR-T therapy. Of the 70% of study participants who received the treatment on an outpatient basis, one-quarter never required hospitalization. Among patients hospitalized during their treatment, the median duration of hospital stay was six days for those treated on an outpatient basis and 15 days for those who received their CAR T-cells as an inpatient.

About half of the participants experienced low-grade CRS, but no patients experienced CRS events of grade three or higher. Rates of neurotoxicity events and infections were both low and in line with those observed in previous trials, indicating that neither outpatient treatment nor the community hospital setting brought any increased risk.

“I encourage as many sites as possible to work on building CAR-T cell programs,” said Dr. Linhares. She added that the successful implementation of CAR T-cell treatment requires a team effort with a high level of coordination among physicians, nurses, and physician assistants; well-delineated standard operating procedures; appropriate labeling in the electronic medical records system; and staff training across multiple hospital departments to ensure any complications are caught and addressed quickly. Moving forward, she suggested that more research could clarify appropriate criteria for determining which patients are best suited for outpatient versus inpatient treatment.

The study did have some limitations, including that tumor burden may have been higher for patients treated on an inpatient basis and that response assessments were performed solely by an investigator, not with the input of an internal review committee. Additionally, the study was not designed with a primary goal of supporting comparisons between inpatients and outpatients.

The study authors expressed hope that the findings will open the door for a much broader array of medical centers to be able to administer CAR-T therapy, avoiding missed opportunities and potentially saving lives by making it feasible for patients to receive the treatment more quickly and closer to home.

This study was funded by Bristol Myers Squibb.

Blood Advances (bloodadvances.org) is an online, open-access journal publishing more peer-reviewed hematology research than any other academic journal worldwide. Blood Advances is part of the Blood journals portfolio (bloodjournals.org) from the American Society of Hematology (ASH) (hematology.org).

Claire Whetzel, 202-629-5085
cwhetzel@hematology.org