FDA Approves Label Update for Axi-Cel for R/R Primary CNS Lymphoma

The FDA has approved a label update for axicabtagene ciloleucel (axi-cel; Yescarta), a CD19-directed autologous T-cell immunotherapy. This update removes previous Limitations of Use for patients with relapsed or refractory (R/R) primary central nervous system lymphoma (PCNSL).¹

Axi-cel is the first and only chimeric antigen receptor (CAR) T-cell therapy approved for R/R large B-cell lymphoma (LBCL) to have this limitation removed, expanding access to a patient population with high unmet clinical needs.

The approval is supported by a phase 1 investigator-sponsored study (NCT04608487)² conducted by the Dana-Farber Cancer Institute, demonstrating a manageable safety profile in patients with PCNSL.

The phase 1 study had a total enrollment of 18 patients (13 with PCNSL and 5 with secondary CNS lymphoma). The primary end point was safety, specifically the rate of treatment-limiting toxicities and grade ≥3 adverse events (AEs). The secondary end points were objective response rate, complete response rate, duration of response, progression-free survival, and overall survival.¹

While the safety profile was deemed manageable, neurologic toxicities remain prevalent, occurring in 85% of patients with PCNSL in the pivotal study, with 31% experiencing grade 3 AEs.

In the PCNSL cohort (n = 13), 85% of patients experienced neurologic toxicities of all grades. Of the total patients in the cohort, 31% experienced grade 3 neurologic toxicities. The median onset of neurotoxicity was 3 days (range, 1-9 days). The median duration was 59 days. Other AEs experienced were hypotension (23%), encephalopathy (15%), seizure (15%), and gait disturbance (8%).

Axi-cel carries a boxed warning regarding cytokine release syndrome (CRS), neurologic toxicities, and secondary hematological malignancies. CRS occurred in 90% of patients with NHL across various studies, with 9% experiencing grade ≥3. Other AEs included fever (85%), hypotension (40%), tachycardia (32%), chills (22%), and hypoxia (20%). Treatment involves tocilizumab (Actemra) or tocilizumab combined with corticosteroids. Two doses of tocilizumab must be available prior to infusion.

PCNSL is a rare, aggressive form of non-Hodgkin lymphoma (NHL) with a poor prognosis; the 5-year survival rate is approximately 30%, and survival following relapse averages only 2 months. Approximately 1500 cases occur annually in the United States, and it accounts for 3% of all primary brain tumors and 1% of all NHL cases. There are currently no standard-of-care treatment options for R/R PCNSL, making it a critical area of unmet medical need.

The FDA's decision to remove the Limitations of Use allows clinicians to prescribe axi-cel to patients with PCNSL who were previously excluded from the clinical trials that supported the therapy's initial approval.

Following the label update, axi-cel is indicated for patients with LBCL, R/R LBCL, R/R follicular lymphoma, and R/R primary CNS lymphoma.

“We are pleased that our study, which highlighted the safety of axi-cel in [CNS] lymphoma, supported the FDA’s decision,” said Lakshmi Nayak, MD, director of the Center for CNS Lymphoma, Dana-Farber Cancer Institute and associate professor of neurology at Harvard Medical School, 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.”

REFERENCES

1.FDA approves label update for Kite’s Yescarta for relapsed/refractory primary central nervous system lymphoma. News release. Kite. Published February 6, 2026. Accessed February 9, 2026. https://tinyurl.com/32kxmw7d

2.Axi-cel in CNS lymphoma. ClinicalTrials.gov. Updated July 30, 2025. Accessed February 9, 2026. https://clinicaltrials.gov/study/NCT04608487