Promising New Data on Kite’s Yescarta® for Relapsed/Refractory CNS Lymphoma

Kite Pharma, a subsidiary of Gilead Sciences, revealed encouraging data from a pilot study evaluating the safety and efficacy of Yescarta® (axicabtagene ciloleucel) in patients with relapsed or refractory primary and secondary central nervous system lymphoma (PCNSL and SCNSL). These findings were presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting.

About CNS Lymphoma

Central nervous system lymphoma (CNSL) is a rare and aggressive form of non-Hodgkin lymphoma that primarily affects the brain, eye, spinal cord, or cerebrospinal fluid. Patients diagnosed with primary CNSL (PCNSL) have historically faced a grim prognosis, with a five-year survival rate of just 30%. Relapse is common, and those affected have a median survival of about two months after initial treatment, underscoring a significant unmet clinical need due to the lack of standard treatment options.

Study Rationale and Design

Dr. Lakshmi Nayak, Associate Professor of Neurology at Harvard Medical School and Director of the Center for CNS Lymphoma at Dana-Farber Cancer Institute, emphasized that patients with central nervous system involvement were excluded from initial studies leading to axi-cel’s FDA approval for relapsed/refractory large B-cell lymphoma. To bridge this gap, the pilot study aimed to assess the safety of axi-cel in CNS lymphoma patients and explore its preliminary efficacy.

Key Outcomes

The study involved 18 patients and had a follow-up period of 24.2 months. Results showed no treatment-limiting toxicities or additional risks of adverse events. Immune effector cell-associated neurologic syndrome (ICANS) was noted in 44% of patients, with 27.8% experiencing grade 3 or higher severity.

The objective response rate was a remarkable 94.4%, with a complete response rate of 66.7%. The median time to best response was three months, and the median duration of response was 13.4 months. Nine patients experienced disease progression, while median progression-free survival was 14.3 months, and median overall survival reached 26.4 months.

Adverse Events
The study found that 90% of patients developed grade 1 or 2 cytokine release syndrome (CRS). Two patients had Ommaya-related meningitis requiring explantation, with subsequent recovery. One patient experienced grade 3 electrographic focal status epilepticus, which resolved with anti-epileptic treatment. Seven patients succumbed to disease progression during the study.

Expert Commentary

Dr. Ibrahim Elhoussieny, Vice President of Medical Affairs at Kite, expressed optimism about the study results, suggesting that CAR T-cell therapy like Yescarta could offer a viable treatment option for patients with relapsed/refractory CNS lymphoma, a group with typically poor prognoses.

Study Details and Endpoints

The study's primary endpoint was safety, determined by treatment-limiting toxicities and the rate of grade 3 or higher adverse events. Secondary endpoints included objective response rate, complete response rate, duration of response, progression-free survival, and overall survival.

Conclusion

The pilot study conducted by Kite Pharma in collaboration with Dana-Farber Cancer Institute provides promising evidence that Yescarta is well-tolerated and potentially effective for patients with relapsed or refractory CNSL. These findings could pave the way for new treatment paradigms for this rare and aggressive form of lymphoma, addressing a critical unmet need in oncology.

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