Phase 2 Study Shows Feasibility of Axi-Cel Delivery in Outpatient Setting

A clinical trial of patients with relapsed or refractory (R/R) large B-cell lymphoma (LBCL) who were treated with axicabtagene ciloleucel (axi-cel) in an outpatient setting achieved response rates consistent with prior trials that evaluated the chimeric antigen receptor (CAR) T-cell therapy in an inpatient setting, according to new results.¹

Findings for ZUMA-24 (NCT05,459571), published August 30, 2025 in the American Journal of Cancer Research, showed patients in the phase 2 trial achieved an objective response rate of 93% and a complete response rate of 76%.¹ Median duration of response was 11.4 months.

The results come nearly 8 years after the axi-cel, sold as Yescarta, received its first FDA approval in October 2017.² Kite, a Gilead company and the maker of axi-cel, sponsored the study as cell and gene therapy manufacturers push o make these therapies more accessible. A decade after the first clinical trials for CAR T-cell therapy, clinicians have become more experienced in their management and the treatments themselves are approved in earlier lines of care.

Most of the 30 patients in ZUMA-24 had received 1 prior line of therapy, including an anti-CD20 monoclonal antibody and an anthracycline-containing che­motherapy regimen; 7 patients had received 2 prior lines of therapy. Patients were excluded if they had received CD19-targeted therapy, any stem cell transplant, or any genetically modified T-cell therapy.¹

Authors, led by Lori A. Leslie, MD, John A. Theurer Cancer Center, Hackensack Meridian Health, New Jersey, outlined the treatment protocol: patients received leukapheresis to obtain mononuclear cells at enrollment, followed by lymphodepleting chemotherapy when they were 5, 4, and 3 days away from infusion. Bridging therapy was given at the investigator’s discretion, no later than 7 days before lymphodepleting chemotherapy. Patients were monitored daily for the first 7 days following infusion with axi-cel (2 x 10⁶ CAR T cells/kg). Prophylactic dexamethasone of 10 mg was given before the axi-cel infusion and on days 1 and 2 after infusion.

During initial monitoring, patients were seen daily at a health care facility in the outpatient setting to evaluate toxicity and vital signs and to complete a neurologic assessment. An optional telemedicine visit was completed at the end of the day. Caregivers or patients contacted the clinic if any prespeci­fied or new abnormalities arose. After 7 days, follow-up at longer intervals was permitted at the investigator’s discretion, although patients had to remain within 2 hours of the clinic for at least 4 weeks.

Additional results showed the following:

• The primary end point was incidence and severity of cytokine release syndrome (CRS) and neurologic events (NEs); median follow-up was 13 months for 30 patients treated with outpatient axi-cel
• Ninety percent of patients had grade 1-2 CRS, with no grade ≥ 3 CRS, and 80% of patients had NEs of any grade, with 23% having grade 3 or higher; no patient deaths were seen due to NEs
• Median time to onset of CRS was 4 to 7 days for NEs, with a median duration of 5 to 6 days, respectively
• All patients experienced adverse events (AEs), with 83% seeing AEs of grade 3 or higher; following axi-cel, 93% of patients were hospitalized (n = 28), with 4 days being the median time to first hospitalization, and a median stay of 8 days
• Most patients (n = 21) were hospitalized for grade 1 events; 4 patients (13%) were admitted to the intensive care unit for 2 to 7 days

In addition, 23 patients completed quality of life (QOL) screening at enrollment and following axi-cel infusion. One patient completed an initial patient-reported outcomes assessment following lymphodepleting chemotherapy and thus did not have an evaluable baseline assessment. For the 22 patients with evaluable data, scores on one QOL scale dropped from baseline at week 4, at the time of axi-cel infusion, and rose above baseline by month 3 following infusion and continued to rise at month 6. Scores on a second QOL scale showed a similar pattern.

The need for patients who are good candidates for CAR T-cell and bispecific therapy to receive treatment closer to home has been much discussed in recent years. This week, panelists addressed the challenge at the Community Oncology Alliance Payer Exchange Summit in Reston, Virginia.³ OneOncology’s Aaron Lyss, MBA, said only 20% of patients eligible for these therapies are gaining access, and costs of care in the community setting are considerably lower than in academic institutions.

The ZUMA-24 trial involved a mix of academic and community centers, including the Greco-Hainsworth Tennessee Oncology Centers for Research, founded by the flagship practice of OneOncology in November 2023.

In June, the FDA eased Risk Evaluation and Mitigation Strategies (REMS) requirements, and community oncology practices are gearing up to make therapies available. However, during the discussion, Humana’s Bryan Loy, MD, MBA, said the FDA’s decision to eliminate the REMS requirement for dual certification for community practices and their hospital partners could make payers ask whether outpatient delivery is safe and effective.³

The ZUMA-24 authors acknowledged some challenges of the outpatient approach. Notably, sending patients home following treatment largely relies on caregivers to notice signs of AEs, even before patients themselves. Increasingly, clinics are using remote monitoring tools to track patients’ responses, and many see this approach as essential to bringing CAR T-cell therapy and bispecifics into community settings. CMS has begun offering community oncology practices reimbursement for remote patient monitoring.

Authors reported on efforts with this approach in ZUMA-24, which enrolled patients between August 2022 and March 2024. They wrote, “The feasibility of central monitoring was investigated through the voluntary use of a wearable device to monitor body temperature and serve as an early warning for the potential onset of AEs. There were challenges with remote monitoring at the sites, and while the device was predictive of AEs, the data were lim­ited due to small sample size and some false positive/false negative results; therefore, inter­pretations of these data are limited.”¹

The authors noted that in other studies involving wearable devices, adherence was above 79%, suggesting strong potential for monitoring.

“In conclusion, this trial demonstrated that out­patient administration of axi-cel was feasible in a multicenter setting. Prophylactic corticosteroids coupled with early intervention, including hospitalization for AE management, resulted in relatively low rates of high-grade toxicities,” they wrote. “Hospital length of stay was shorter than in pre­vious clinical trials with inpatient administra­tion of axi-cel, which could translate to more efficient use of health care resources and alleviate capacity constraints on care.”

References

1. Leslie LA, Baird JH, Flinn IW, et al. Outpatient axicabtagene ciloleucel for relapsed/refractory large B-cell lymphoma: ZUMA-24 primary analysis. Am J Cancer Res. 2025;15(8):3417-3433. doi:10.62347/GJNN1023
2. FDA approves axicabtagene ciloleucel for large B-cell lymphoma. News release. FDA. October 25, 2017. Accessed September 13, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-axicabtagene-ciloleucel-large-b-cell-lymphoma
3. Caffrey M. FDA change smooths way for bispecific access in community practice. AJMC^®. September 9, 2025. Access September 13, 2025 https://www.ajmc.com/view/fda-change-smooths-way-for-bispecific-access-in-community-practice