The FDA has updated the safety labeling for axicabtagene ciloleucel (Yescarta, Kite Oncology) ­— a CAR T-cell therapy — extending its indication to include patients with relapsed or refractory primary central nervous system lymphoma (R/R PCNSL).

Axicabtagene ciloleucel, also known as axi-cel, is a CD19-directed genetically modified autologous T-cell immunotherapy indicated for certain adults with relapsed or refractory large B-cell lymphoma or follicular lymphoma.

Previous labeling listed R/R PCNSL in a Limitations of Use section stating that the therapy “is not indicated for the treatment of patients with primary central nervous system lymphoma.” However, positive results from a phase 1 study including patients with R/R PCNSL prompted the labeling change, the company announced in a press release.

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

PCNSL is a rare and fast‑growing lymphoma that originates in the brain, spinal cord, eye, or cerebrospinal fluid, and it has a poor prognosis. 

The 5‑year survival rate is about 30%, and more than half of patients have disease recurrence after their treatment, the company explained, noting that the “subsequent survival of approximately two months [highlights] the urgent need for new and better treatment options.” 

The phase 1 safety study included 13 patients with R/R PCNSL. Preliminary data presented at the 2024 American Society of Clinical Oncology meeting showed that about half of the treated patients were alive and relapse-free at 1 year. 

Neurologic toxicities occurred in 85% (11/13) of patients, and 31% had grade 3 neurologic toxicities. Grade 3 or 4 adverse events were hypotension (23%), encephalopathy (15%), seizure (15%), gait disturbance (8%), headache (8%), hypoxia (8%), muscular weakness (8%), nausea (8%), pyrexia (8%), thrombosis (8%), and tremor (8%), Nayak and colleagues found. 

“We are encouraged by the positive results of the safety study in patients with central nervous system lymphoma, who were previously excluded from the trials supporting Yescarta’s approval,” Gallia Levy, MD, PhD, Kite’s senior vice president and global head of development, stated in the company press release. 

“Most CAR T-cell trials had excluded patients with CNS involvement because neurologic toxicity is a known risk of CD19 CAR T therapy, raising concerns that side effects could be more pronounced when lymphoma is in the brain,” Dana-Farber further explained in a separate press release. “At the same time, early experiences in select lymphoma studies and in acute lymphoblastic leukemia suggested CAR T cells can enter the CNS and have anti-tumor activity, underscoring the need for prospective data in this population.” 

Sharon Worcester, MA, is an award-winning medical journalist based in Birmingham, Alabama, writing for Medscape, MDedge and other affiliate sites. She currently covers oncology, but she has also written on a variety of other medical specialties and healthcare topics. She can be reached at sworcester@mdedge.com or on X: @SW_MedReporter.