Dana-Farber Research Helps Drive FDA Label Update for Primary CNS Lymphoma

Change removes prior exclusion and may expand access to CAR T-cell therapy for eligible relapsed or refractory patients

Dana-Farber Cancer Institute-led research helped drive an FDA label update for axicabtagene ciloleucel (Yescarta) that removes a prior exclusion for patients with primary central nervous system lymphoma, a rare and aggressive lymphoma of the brain and spinal cord. The change is expected to expand access to commercial CAR T-cell therapy for eligible patients with relapsed or refractory disease.

The updated labeling reflects years of Dana-Farber research focused on defining whether CD19-directed CAR T-cell therapy can be delivered safely and effectively to patients with lymphoma involving the central nervous system. 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. 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.

“This creates an opportunity for patients to have access to commercial CAR T-cell therapy when it didn’t exist for them before, specifically for patients with relapsed or refractory primary lymphomas of the brain and spinal cord,” said Dr. Caron Jacobson, Medical Director of Dana-Farber’s Immune Effector Cell Therapy Program. “To have an investigator-initiated study lead to an FDA label change was really unimaginable, and it’s been the most gratifying moment of my professional career because it can directly change what’s possible for patients.”

Dana-Farber launched a pilot, investigator-initiated study to test the safety and feasibility of CAR T-cell therapy in patients with relapsed or refractory primary and secondary CNS lymphoma and to look for an efficacy signal strong enough to justify larger studies. The trial enrolled 18 patients and was conducted in stages with careful monitoring for treatment-limiting toxicities. Data from the study were ultimately used to support the FDA’s decision that the prior primary CNS lymphoma exclusion was unnecessary.
This change means that eligible patients with diffuse large B-cell lymphoma confined to the central nervous system are no longer automatically excluded from receiving commercially available axi-cel simply because of where the lymphoma is located. It opens the door for eligible primary CNS lymphoma patients to be considered for CAR T-cell therapy after one or more prior lines of treatment, consistent with the treatment’s use in the relapsed or refractory setting.

Dr. Lakshmi Nayak presented encouraging outcomes in this hard-to-treat population, at the 2024 ASCO Annual Meeting, showing that approximately half of treated patients were alive and without relapse at around one year, while also noting that some late relapses occurred and longer follow-up is needed to understand how many patients may achieve long-term remission. 

"This is a historic milestone for a rare and aggressive brain tumor that has had no FDA-approved therapies”, said Nayak, director of the Center for CNS Lymphoma at Dana-Farber. “Our results and the FDA’s decision offer hope to patients with primary CNS lymphoma for the very first time”.