FDA Updates Axi-Cel Label to Remove Limitation of Use in R/R PCNSL

The FDA has approved an update to the prescribing information for axicabtagene ciloleucel (axi-cel; Yescarta), removing the prior Limitations of Use for patients with relapsed/refractory primary central nervous system lymphoma (PCNSL).¹

With this revision, axi-cel is now the only CAR T-cell therapy approved for R/R large B-cell lymphoma to have this limitation removed, reinforcing the therapy’s safety profile in eligible patients with relapsed/refractory PCNSL. The FDA’s decision was supported by positive findings from an investigator-sponsored phase 1 study (NCT04608487) conducted at Dana-Farber Cancer Institute, which evaluated axi-cel in patients with relapsed/refractory PCNSL. In the phase 1 trial, neurologic toxicities were reported in 85% of treated patients (n = 13), with grade 3 neurologic adverse effects (AEs) occurring in 31% of patients. Reported grade 3 or 4 AEs included hypotension (23%), encephalopathy (15%), and seizure (15%); gait disturbance, headache, hypoxia, muscular weakness, nausea, pyrexia, thrombosis, and tremor were all reported in 1 patient each (8%).

“We are pleased that our study, which highlighted the safety of axi-cel in CNSL, supported the FDA’s decision,” Lakshmi Nayak, MD, director of the Center for CNS Lymphoma at Dana-Farber Cancer Institute and associate professor of neurology at Harvard Medical School, stated in a news release. “This update to the axi-cel prescribing information provides clinicians with important evidence for patients who have historically had very limited treatment options.”

Despite the high incidence of neurologic AEs, the FDA concluded that the overall safety profile supported removal of the prior labeling restriction, marking an important regulatory milestone for CAR T-cell therapy in PCNSL.

“We are encouraged by the positive results of the safety study in patients with CNSL, who were previously excluded from the trials supporting [axi-cel’s] approval,” Gallia Levy, MD, PhD, senior vice president and global head of Development at Kite, added in a news release. “We appreciate the FDA’s timely review and decision, which expands access to [axi-cel] for patients with PCNSL—one of the most aggressive and underserved forms of the disease and we are deeply grateful to the patients and clinicians who made this progress possible.”

What are axi-cel’s approved indications?

Axi-cel is currently approved in the following indications:

• For adult patients with large B-cell lymphoma that is refractory to first-line chemoimmunotherapy or that relapses within 12 months of first-line chemoimmunotherapy.
• For adult patients with relapsed or refractory large B-cell lymphoma (LBCL) after 2 or more lines of systemic therapy, including diffuse LBCL (DLBCL) not otherwise specified, primary mediastinal LBCL, high grade B-cell lymphoma, and DLBCL arising from follicular lymphoma.
• For adult patients with relapsed or refractory follicular lymphoma after two or more lines of systemic therapy (accelerated approval)

How was this phase 1 study designed?

The investigator-sponsored phase 1 study was designed as a safety-focused evaluation of axi-cel in CNS lymphoma, enrolling 18 patients overall, including 13 with PCNSL and 5 with secondary CNS lymphoma.² The protocol incorporated an initial safety run-in, in which the first 6 treated patients were observed for treatment-limiting toxicities (TLTs) to characterize early tolerability in this higher-risk population.

The primary end point was safety, assessed by the rate of TLTs and the incidence of grade 3 or higher AEs. Secondary end points included objective response rate, complete response rate, duration of response, progression-free survival, and overall survival.

What box warnings are associated with axi-cel?

Axi-cel carried a boxed warning for cytokine release syndrome (CRS), neurologic toxicities, and secondary hematologic malignancies, reflecting known risks associated with CD19-directed CAR T-cell therapy.¹ CRS, including fatal or life-threatening events, has been observed following axi-cel infusion, and axi-cel should not be administered to patients with active infection or uncontrolled inflammatory disorders. Severe or life-threatening CRS requires prompt management with tocilizumab, with or without corticosteroids.

Neurologic toxicities, including encephalopathy, seizures, and other severe or fatal events—have also been reported and may occur concurrently with CRS, following CRS resolution, or independently. Patients treated with axi-cel require close neurologic monitoring after infusion, with supportive care and corticosteroids administered as clinically indicated. In addition, cases of secondary T-cell malignancies have been reported following treatment with genetically modified autologous T-cell immunotherapies targeting CD19 or BCMA, including axi-cel, underscoring the need for long-term surveillance.

References

1. FDA approves label update for Kite’s Yescarta for relapsed/refractory primary central nervous system lymphoma. News Release. Kite, a Gilead Company. February 06, 2026 Accessed February 06, 2026. https://www.kitepharma.com/news/press-releases/2026/2/fda-approves-label-update-for-kites-yescarta-for-relapsedrefractory-primary-central-nervous-system-lymphoma
2. Axi-cel in CNS lymphoma. ClinicalTrials.gov. Updated July, 30, 2025. Accessed January 6, 2026. https://clinicaltrials.gov/study/NCT04608487